RESUMEN

BACKGROUNDS AND OBJECTIVE: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are pivotal in managing hypercholesterolemia and reducing cardiovascular risk. While rosuvastatin demonstrates superior efficacy and tolerability compared to other statins, its safety profile in elderly patients older than 75 years old with acute coronary syndrome (ACS) remains underexplored. So, the objective of this study is to evaluate the frequency of adverse reactions and investigate the efficacy of high-dose rosuvastatin on lipid profiles in elderly patients aged over 75 with ACS. METHODS: In this observational study, 110 consecutive elderly ACS patients attending Modarres Hospital in Tehran, Iran, in 2019 were enrolled. The effects of high-dose rosuvastatin were assessed in elderly patients older than 75 years old by comparison of the adverse effects, lipid profile, cardiac function, and other biomarkers at the baseline and after 6 weeks of rosuvastatin therapy with a dose of 40 mg. RESULTS: Following 6 weeks of treatment, there was a significant reduction in total cholesterol (136.2 ± 24.3 to 115.5 ± 24.0, p = 0.001) and LDL levels (72.6 ± 17.5 to 50.9 ± 18.9, p = 0.001), accompanied by a notable increase in HDL levels (38.3 ± 7.1 to 47.2 ± 7.4, p = 0.001). Cardiac function, as measured by ejection fraction (EF), significantly improved from 43.4 ± 8.8 to 48.5 ± 8.5 (p = 0.001). Adverse effects such as cramps (N = 12, p = 0.001), weakness (N = 28, p = 0.001), and anorexia (N = 12, p = 0.001) were reported but did not warrant discontinuation of therapy. Notably, no cases of jaundice were observed. Two deaths occurred due to major adverse cardiac events (MACE) during the study period, unrelated to stroke or recurrent myocardial infarction. CONCLUSION: Totally, high-dose rosuvastatin therapy effectively improved lipid profiles, cardiac function, and liver enzyme levels in elderly ACS patients, with manageable adverse effects. These findings underscore the importance of rosuvastatin in optimizing cardiovascular health in this vulnerable population.

Asunto(s)

Síndrome Coronario Agudo , Biomarcadores , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/efectos adversos , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Anciano , Masculino , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Resultado del Tratamiento , Anciano de 80 o más Años , Irán , Biomarcadores/sangre , Factores de Tiempo , Factores de Edad , Dislipidemias/tratamiento farmacológico , Dislipidemias/diagnóstico , Dislipidemias/sangre , Lípidos/sangre , Estudios Prospectivos

RESUMEN

Futibatinib, an inhibitor of fibroblast growth factor receptor 1-4, is approved for the treatment of patients with advanced cholangiocarcinoma with FGFR2 fusions/rearrangements. In this phase I drug-drug interaction study, the effects of futibatinib on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates, and of P-gp inhibition on futibatinib pharmacokinetics (PK) were investigated in healthy adults aged 18-55 years. In part 1, 20 participants received digoxin (P-gp substrate) and rosuvastatin (BCRP substrate). Following a ≥10-day washout, futibatinib was administered for 7 days, with digoxin and rosuvastatin coadministered on the third day. In part 2, 24 participants received futibatinib. Following a ≥3-day washout, quinidine (P-gp inhibitor) was administered for 4 days, with futibatinib coadministered on day 4. Blood samples were collected predose and for 24 (futibatinib), 72 (rosuvastatin), and 120 h (digoxin) postdose. Urine samples (digoxin) were collected predose and for 120 h postdose. PK parameters were compared between treatments using analysis of variance. Coadministration with futibatinib had no effect on the PK of digoxin and rosuvastatin, and coadministration with quinidine had minimal effects on the PK of futibatinib. Differences in Cmax and AUC with and without futibatinib and quinidine, respectively, were <20%. The most common treatment-emergent adverse events were diarrhea (80%) and increased blood phosphorous (75%) in part 1 and prolonged electrocardiogram QT interval (38%) in part 2. The data show that futibatinib has no clinically meaningful effects on the PK of P-gp or BCRP substrates and that the effect of P-gp inhibition on futibatinib PK is not clinically relevant.

Asunto(s)

Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Digoxina , Interacciones Farmacológicas , Proteínas de Neoplasias , Rosuvastatina Cálcica , Humanos , Adulto , Masculino , Femenino , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Persona de Mediana Edad , Adulto Joven , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administración & dosificación , Adolescente , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Digoxina/farmacocinética , Digoxina/administración & dosificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Voluntarios Sanos , Área Bajo la Curva , Subfamilia B de Transportador de Casetes de Unión a ATP/antagonistas & inhibidores , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo

RESUMEN

After oral administration, the intestine is the first site of drug absorption, making it a key determinant of the bioavailability of a drug, and hence drug efficacy and safety. Existing non-clinical models of the intestinal barrier in vitro often fail to mimic the barrier and absorption of the human intestine. We explore if human enteroid monolayers are a suitable tool for intestinal absorption studies compared to primary tissue (Ussing chamber) and Caco-2 cells. Bidirectional drug transport was determined in enteroid monolayers, fresh tissue (Ussing chamber methodology) and Caco-2 cells. Apparent permeability (Papp) and efflux ratios for enalaprilat (paracellular), propranolol (transcellular), talinolol (P-glycoprotein (P-gp)) and rosuvastatin (Breast cancer resistance protein (BCRP)) were determined and compared between all three methodologies and across intestinal regions. Bulk RNA sequencing was performed to compare gene expression between enteroid monolayers and primary tissue. All three models showed functional efflux transport by P-gp and BCRP with higher basolateral to apical (B-to-A) transport compared to apical-to-basolateral (A-to-B). B-to-A Papp values were similar for talinolol and rosuvastatin in tissue and enteroids. Paracellular transport of enalaprilat was lower and transcellular transport of propranolol was higher in enteroids compared to tissue. Enteroids appeared show more region- specific gene expression compared to tissue. Fresh tissue and enteroid monolayers both show active efflux by P-gp and BCRP in jejunum and ileum. Hence, the use of enteroid monolayers represents a promising and versatile experimental platform to complement current in vitro models.

Asunto(s)

Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Absorción Intestinal , Propranolol , Rosuvastatina Cálcica , Humanos , Células CACO-2 , Rosuvastatina Cálcica/farmacocinética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Propranolol/farmacocinética , Propranolol/metabolismo , Permeabilidad , Mucosa Intestinal/metabolismo , Enalaprilato/farmacocinética , Enalaprilato/metabolismo , Transporte Biológico , Organoides/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Propanolaminas/farmacocinética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Masculino

RESUMEN

BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.

Asunto(s)

Atorvastatina , Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/efectos adversos , Rosuvastatina Cálcica/uso terapéutico , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Femenino , Persona de Mediana Edad , Anciano , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Incidencia , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Biomarcadores/sangre , Medición de Riesgo

RESUMEN

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan-Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024-1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

Asunto(s)

Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Infarto del Miocardio , Humanos , Infarto del Miocardio/tratamiento farmacológico , Masculino , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Persona de Mediana Edad , Anciano , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/efectos adversos , República de Corea/epidemiología , Atorvastatina/administración & dosificación , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Sistema de Registros , Incidencia

RESUMEN

Toxoplasma gondii (T.gondii) is an obligate intracellular protozoan that infects warm-blooded animals and has a global distribution. Acute toxoplasmosis is commonly reported in patients with acquired/congenital toxoplasmosis and immune deficiency. New methods are needed to prevent the sideffects of classical treatment. In this study, Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS) were synthesized and zeta potential and size were determined, and an MTT assay was performed to evaluate the cell toxicity on Macrophage cells (MQ) and anti-Toxoplasma activity using Trypan-blue staining by different concentrations of Rosuvastatin (ROS), and Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS). The cell viability assay demonstrated that CH-NP-ROS had lower cell toxicity (<15 %) compared to ROS (<30 %). Statistical analysis showed that CH-NP-ROS significantly killed 98.950 ± 1.344; P < 0.05) of Toxoplasma gondii tachyzoites. In vivo results of perituneal fluid showed that CH-NP significantly reduced the parasite load in the CH-NP-ROS group, compared to that in negative control group (P < 0.001). Growth inhibition rates of tachyzoites in mice receiving free ROS and CH-NP-ROS (injection and oral form) were found to be 166.125 + 4.066, 118.750 + 4.596 and 124.875 + 2.652, respectively, compared to mice in Sulfadiazine/Pyrimethamine treated group (positive control). In the infected untreated mice (control +), the mean tachyzoite counts per oil immersion field in the spleen was 8.25 respectively. The mean survival time in all the groups treated with ROS and CH-NP-ROS was longer than that in the negative control group Therefore, nanoformulation is a promising approach for the delivery and is safe for using therapeutic effects in acute toxoplasmosis.

Asunto(s)

Quitosano , Nanopartículas , Rosuvastatina Cálcica , Toxoplasma , Toxoplasmosis , Animales , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/administración & dosificación , Nanopartículas/química , Toxoplasma/efectos de los fármacos , Ratones , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/parasitología , Supervivencia Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Carga de Parásitos , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Modelos Animales de Enfermedad , Portadores de Fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Toxoplasmosis Animal/parasitología , Femenino , Ratones Endogámicos BALB C

RESUMEN

Background: Monitoring noncommunicable diseases is regarded as a critical concern that has to be managed in order to avoid a wide variety of complications such as increasing blood lipid levels known as dyslipidemia. Statin drugs, mostly, Rosuvastatin (RSV) was investigated for its effectiveness in treating dyslipidemia. However, reaching the most efficient treatment is essential and improving the effect of RSV is crucial. Therefore, a combination therapy was a good approach for achieving significant benefit. Although RSV is hydrophobic, which would affect its absorption and bioavailability following oral administration, overcoming this obstacle was important. Purpose: To that end, the purpose of the present investigation was to incorporate RSV into certain lipid-based nanocarriers, namely, nanostructured lipid carrier (NLC) prepared with virgin coconut oil (CCO). Methods: The optimized RSV-NLC formula was selected, characterized and examined for its in vitro, kinetic, and stability profiles. Eventually, the formula was investigated for its in vivo hypolipidemic action. Results: The optimized NLC formulation showed a suitable particle size (279.3±5.03 nm) with PDI 0.237 and displayed good entrapment efficiency (75.6±1.9%). Regarding in vitro release, it was efficiently prolonged for 24 h providing 93.7±1.47%. The optimized formula was established to be stable after 3 months storage at two different conditions; 4°C and 25°C. Importantly, including CCO in the development of RSV-NLC could impressively enhance lowering total cholesterol level in obese rat models, which endorse the potential synergistic action between RSV and CCO. Conclusion: The study could elucidate the impact of developing NLC using CCO for improving RSV anti-hyperlipidemic activity.

Asunto(s)

Aceite de Coco , Portadores de Fármacos , Hipolipemiantes , Nanoestructuras , Tamaño de la Partícula , Rosuvastatina Cálcica , Animales , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/administración & dosificación , Aceite de Coco/química , Aceite de Coco/farmacología , Hipolipemiantes/química , Hipolipemiantes/farmacología , Hipolipemiantes/farmacocinética , Hipolipemiantes/administración & dosificación , Portadores de Fármacos/química , Masculino , Ratas , Nanoestructuras/química , Lípidos/química , Lípidos/sangre , Ratas Wistar , Liberación de Fármacos , Disponibilidad Biológica , Administración Oral

RESUMEN

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].

Asunto(s)

Enfermedades Cardiovasculares , Infecciones por VIH , Análisis de la Onda del Pulso , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/administración & dosificación , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Persona de Mediana Edad , Método Doble Ciego , Placebos/administración & dosificación , Adulto , Sulfonamidas/uso terapéutico , Sulfonamidas/farmacología , Resultado del Tratamiento , Pirimidinas , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fluorobencenos/uso terapéutico

Asunto(s)

Infecciones por VIH , Rosuvastatina Cálcica , Rigidez Vascular , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Masculino , Rigidez Vascular/efectos de los fármacos , Rosuvastatina Cálcica/efectos adversos , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/administración & dosificación , Persona de Mediana Edad , Adulto , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Resultado del Tratamiento

RESUMEN

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy. Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites. Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium_coprostanoligenes and g-Papillibacter, while the characteristic flora of the BS group were o-C0119, g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-ß-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism. Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins.

Asunto(s)

Enfermedad Coronaria , Microbioma Gastrointestinal , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bacterias/metabolismo , Ácidos y Sales Biliares/metabolismo , Biomarcadores/sangre , Estudios de Casos y Controles , China , LDL-Colesterol/sangre , LDL-Colesterol/metabolismo , Enfermedad Coronaria/microbiología , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/metabolismo , Pueblos del Este de Asia , Heces/microbiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Metabolómica , ARN Ribosómico 16S/genética , Rosuvastatina Cálcica/uso terapéutico , Resultado del Tratamiento

RESUMEN

Cardiotoxicity is a side effect of chemotherapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients receiving both anthracyclines and trastuzumab. We looked for a possible protective effect of rosuvastatin against chemotherapy-induced cardiotoxicity. Methods: 50 newly diagnosed HER2 positive breast cancer patients were randomly allocated into two groups: 25patients in each. Group 1(control group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy. Group 2 (treatment group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy and 20 mg of oral rosuvastatin 24 h before the first cycle of chemotherapy and once daily for the rest of the follow-up period (6 months). Transthoracic echocardiography was done, and blood samples were collected for patients 24 h before the initiation of therapy, after 3 months and after 6 months to assess serum levels of high sensitivity cardiac troponin I (hs-cTnI), Myeloperoxidase (MPO), Interleukin-6 (IL-6) and Alanine aminotransferase (ALT). The study was retrospectively registered in Clinical Trials.gov in April 2022. Its ID is NCT05338723. Compared to control group, Rosuvastatin-treated group had a significantly lower decline in LVEF after 3 months and after 6 months. They had significantly lower Hs-cTnI and IL-6 after 3 months and after 6 months, and significantly lower MPO after 6 months. Four patients in control group experienced cardiotoxicity while no one in rosuvastatin-treated group. Rosuvastatin attenuated cardiotoxicity, so it is a promising protective agent against chemotherapy-induced cardiotoxicity.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Cardiotoxicidad , Doxorrubicina , Receptor ErbB-2 , Rosuvastatina Cálcica , Trastuzumab , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Rosuvastatina Cálcica/uso terapéutico , Femenino , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Doxorrubicina/efectos adversos , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Troponina I/sangre

RESUMEN

The patient was a 54-year-old woman with familial hypercholesterolemia and remarkable Achilles tendon thickening. At 20 years old, the patient had a total cholesterol level of approximately 300 mg/dL. She started receiving rosuvastatin (5 mg/day) for low-density lipoprotein cholesterol (LDL-C) 235 mg/dL at 42 years old, which was increased to 10 mg/day at 54 years old, decreasing her serum LDL-C level to approximately 90 mg/dL. The serum Lp (a) level was 9 mg/dL. A computed tomography coronary angiogram showed no significant stenosis. Next-generation sequencing revealed a frameshift variant in LDL receptor (LDLR) (heterozygous) and a missense variant in proprotein convertase subtilisin/kaxin type 9 (PCSK9) (heterozygous). Continued statin therapy, in addition to low Lp (a) and female sex, can help prevent cardiovascular disease.

Asunto(s)

Tendón Calcáneo , Hiperlipoproteinemia Tipo II , Proproteína Convertasa 9 , Receptores de LDL , Humanos , Tendón Calcáneo/diagnóstico por imagen , Tendón Calcáneo/patología , Femenino , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Receptores de LDL/genética , Persona de Mediana Edad , Proproteína Convertasa 9/genética , Rosuvastatina Cálcica/uso terapéutico , Aterosclerosis/genética , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , LDL-Colesterol/sangre , Mutación Missense , Japón , Pueblos del Este de Asia

RESUMEN

The prevalence of metabolic dysfunction associated-steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease; NAFLD) is estimated at around 32% of the world's population, resulting in a major healthcare concern in recent times. Current pharmaceutical methods lack efficacy for the treatment of the disease because of suboptimal pharmacokinetic parameters including poor bioavailability, short half-life, and premature clearance. Designing an efficient drug delivery system that provides a protective environment is critical for addressing these challenges. Such a system should aim to enhance the cellular uptake of drugs, improve their bioavailability, and reduce the chances of rapid clearance. Here, we developed nanoengineered natural cell membrane-derived nanoparticles (CMNs) incorporated with a model drug, rosuvastatin, in the bilayer assembly of CMNs to reduce the accumulation of lipids in hepatocytes, a hallmark of MASLD. We used a cell extrusion technique to develop self-assembled CMNs with precise size control compared to the cell shearing method. Interestingly, the prepared CMNs were found to be nonphagocytic, representing around 1.13% of phosphatidylserine receptors on healthy cells, which allows the possibility of their use as stealth nanoparticles for drug delivery. Furthermore, CMNs exhibit higher drug-loading efficiency, excellent cytocompatibility, and enhanced cellular internalization capabilities. Moreover, we show that the delivery of rosuvastatin-loaded CMNs in the in vitro MASLD model efficiently reduced hepatocyte lipid accumulation, including total cholesterol (26.8 ± 3.1%) and triglycerides (11.8 ± 0.8%), compared to the negative control. Taken together, the nanoengineered biomimetic CMNs enhance the drug's bioactivity in hepatic cells, establishing a foundation for further investigation of this drug delivery system in treating MASLD.

Asunto(s)

Materiales Biomiméticos , Membrana Celular , Nanopartículas , Enfermedad del Hígado Graso no Alcohólico , Rosuvastatina Cálcica , Humanos , Nanopartículas/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Rosuvastatina Cálcica/química , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/farmacocinética , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Células Hep G2 , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Sistemas de Liberación de Medicamentos

RESUMEN

Aims/Background Rosuvastatin is a common lipid-lowering statin on the market, but its impact on the incidence of long-term cardiovascular events is not well clarified. This study aimed to explore the effects of rosuvastatin on serum asymmetric dimethylarginine (ADMA) levels and the incidence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension. Methods This retrospective study included 158 patients with hyperlipidaemia and H-type hypertension who were treated in the Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine from August 2015 to August 2016. The patients were divided into an occurrence group and a non-occurrence group according to the occurrence of long-term cardiovascular events following the resuvostatin treatment. The changes in blood lipids, blood pressure, serum ADMA levels and vascular endothelial function indexes before and after treatment were compared, and the effect of ADMA on the occurrence of long-term cardiovascular events and its predictive efficacy were analysed using the Spearman correlation test and receiver operating characteristics (ROC) curve. Results After treatment, the levels of serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, serum ADMA and blood pressure became significantly lower (p < 0.001), with high-density lipoprotein cholesterol exhibiting no significant difference. Twenty-two cases developed long-term cardiovascular events after the treatment, with an incidence of 13.92%. The occurrence group had significantly higher serum ADMA levels than the non-occurrence group (p < 0.001). The rosuvastatin treatment also lowered the levels of endothelin-1 and high-sensitivity C-reactive protein and increased the nitric oxide level (p < 0.001). Spearman correlation analysis showed that serum ADMA levels were positively correlated with the occurrence of long-term cardiovascular events (r=0.462, p < 0.001). Meanwhile, according to the ROC curve, serum ADMA had a good predictive efficacy for long-term cardiovascular events, with an area under the curve of 0.885 (95% confidence interval 0.808-0.963; p < 0.001). Conclusion Rosuvastatin can reduce ADMA levels and exert vascular protective effects. The increase in serum ADMA levels is closely related to the occurrence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension, serving as a potential clinical predictor to guide disease prevention and treatment.

Asunto(s)

Arginina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipidemias , Hipertensión , Rosuvastatina Cálcica , Humanos , Arginina/análogos & derivados , Arginina/sangre , Rosuvastatina Cálcica/uso terapéutico , Masculino , Femenino , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Hiperlipidemias/epidemiología , Hiperlipidemias/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Hipertensión/tratamiento farmacológico , Hipertensión/sangre , Hipertensión/epidemiología , Hipertensión/complicaciones , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , Incidencia , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/sangre , Presión Sanguínea/efectos de los fármacos

RESUMEN

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.

Asunto(s)

Inhibidores de Hidroximetilglutaril-CoA Reductasas , Nanopartículas , Transportadores de Anión Orgánico Sodio-Dependiente , Rosuvastatina Cálcica , Simportadores , Animales , Nanopartículas/química , Transportadores de Anión Orgánico Sodio-Dependiente/antagonistas & inhibidores , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Simportadores/antagonistas & inhibidores , Simportadores/metabolismo , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/química , Rosuvastatina Cálcica/administración & dosificación , Humanos , Ratones Endogámicos C57BL , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/química , Colesterol/química , Ratas Sprague-Dawley , Ratones

RESUMEN

INTRODUCTION: Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy. METHODS: A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence). RESULTS: A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001). CONCLUSIONS: This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

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Lipid-lowering therapy to control low-density lipoprotein (LDL) cholesterol levels is essential for cardiovascular risk prevention. Successful therapy depends on the type of lipid-lowering therapy, i.e., low or high statin intensity and combination of statins with ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and adherence to therapy, i.e., whether the patient actually takes their pills as prescribed. If there are fewer pills to be taken, this can help patients to follow their treatment. Single-pill combinations of two drugs could facilitate adherence and thus the chances of reaching the recommended lipid targets. Here, we analyzed a sample of Italian patients with dyslipidemia to examine whether the switch from a free combination of two separate pills of rosuvastatin and ezetimibe to a single-pill combination of the same drugs could improve adherence to therapy. We found that the proportion of adherent patients increased from about just over half (51.8%) to about three-fourths (75.1%) when switching from two-pill to single-pill combination of rosuvastatin and ezetimibe. These findings suggest that simplifying therapy can help improve patient adherence, which is essential for reaching lipid targets and ultimately for alleviating atherosclerotic cardiovascular disease.

Asunto(s)

Combinación de Medicamentos , Ezetimiba , Cumplimiento de la Medicación , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/administración & dosificación , Ezetimiba/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Masculino , Femenino , Estudios Retrospectivos , Italia , Anciano , Persona de Mediana Edad , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/administración & dosificación , Quimioterapia Combinada , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico

RESUMEN

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA). Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study. Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects. Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.

Asunto(s)

Amlodipino , Estudios Cruzados , Combinación de Medicamentos , Ezetimiba , Voluntarios Sanos , Rosuvastatina Cálcica , Telmisartán , Humanos , Telmisartán/administración & dosificación , Telmisartán/farmacocinética , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administración & dosificación , Amlodipino/farmacocinética , Amlodipino/administración & dosificación , Masculino , Ezetimiba/administración & dosificación , Ezetimiba/farmacocinética , Adulto , Adulto Joven , Benzoatos/farmacocinética , Benzoatos/administración & dosificación , Bencimidazoles/farmacocinética , Bencimidazoles/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas

RESUMEN

microRNAs are candidate diagnostic biomarkers for Alzheimer's disease. This study aimed to compare Silymarin with Rosuvastatin and placebo on total-Tau protein level and expression levels of microRNAs and TGF-ß and COX-2 in Alzheimer's patients with secondary dyslipidemia. 36 mild AD patients with dyslipidemia were divided into three groups of 12. The first group received silymarin (140mg), the second group received placebo (140mg), and the third group recieved Rosuvastatin (10mg). Tablets were administered three times a day for Six months. The blood samples of the patients were collected before and after the intervention and the serum was separated. Using the RT-qPCR method, the expression levels of miR-124-3p and miR-125b-5p were assessed, and the serum levels of total-Tau, TGF-ß, and COX-2 enzyme were measured using the ELISA method. Data were analyzed with SPSS software. In this study, the level of Δtotal-Tau was significantly lower in the Rosuvastatin group compared to the placebo (P = 0.038). Also, a significant reduction in the level of ΔTGF-ß was observed in the Silymarin to Rosuvastatin group (p = 0.046) and ΔmiR-124-3p was significantly increased in the Rosuvastatin compared to the placebo group (p = 0.044). Rosuvastatin outperformed silymarin in decreasing Δtotal-Tau serum levels and enhancing expression of ΔmiR-124-3p, attributed to Rosuvastatin's capacity to lower cholesterol levels and inflammation concurrently. Conversely, silymarin was more effective than Rosuvastatin in reducing levels of ΔTGF-ß. Serum miR-124-3p could serve as a promising diagnostic biomarker and a new therapeutic focus in AD.

Asunto(s)

Enfermedad de Alzheimer , Dislipidemias , MicroARNs , Rosuvastatina Cálcica , Proteínas tau , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Estudios de Cohortes , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , MicroARNs/sangre , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/uso terapéutico , Proteínas tau/sangre

RESUMEN

OBJECTIVES: Atherosclerotic cardiovascular disease (ASCVD) events have been shown to occur at higher frequency in patients with peripheral arterial disease (PAD). In this study, our aim is to evaluate whether statin is being used appropriately in patients with PAD and also evaluate its usage with the number of vascular beds involved. MATERIALS AND METHODS: This retrospective cross-sectional study reviewed data of patients with a confirmed diagnosis of PAD based on invasive or noninvasive imaging. Demographic, clinical, laboratory, and treatment data collected were described using descriptive statistics. Multiple logistic regression analysis was conducted to determine the predictors for the prescription of statins (HIS). High-intensity statin therapy was defined as atorvastatin ≥40 mg per day, rosuvastatin ≥20 mg per day, or simvastatin ≥80 mg per day, according to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. RESULTS: We analyzed data from 166 patients who met the inclusion criteria. The mean age was 63.34 years. The most common comorbidity was diabetes mellitus (DM) (68.86%). Statins were used in 82% of patients, among whom only 39% were on high-intensity statins. Multiple logistic regression analysis revealed that patients with cerebrovascular disease (CVD) [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.06-0.61, p = 0.005], on oral anticoagulants (OAC) (OR = 0.16, 95% CI = 0.04-0.62, p = 0.008) and on dual antiplatelet therapy (DAPT) (OR = 0.20, 95% CI = 0.08-0.47, p < 0.000) had lower odds of receiving lower extremity revascularization (LIS) therapy. CONCLUSION: Despite having a high risk of future adverse cardiac events, patients with PAD are less likely to receive appropriate statin therapy. Involvement of more vascular beds was associated with higher chances of initiating high-intensity statin.

Asunto(s)

Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Masculino , Femenino , Estudios Transversales , Estudios Retrospectivos , Anciano , Rosuvastatina Cálcica/uso terapéutico , Atorvastatina/uso terapéutico

RESUMEN

BACKGROUND: Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP). HYPOTHESIS: The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP. METHODS: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%). RESULTS: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (ß = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (ß = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (ß = -0.300, p < 0.001) and intensive statin therapy (ß = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C. CONCLUSIONS: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels.

Asunto(s)

Biomarcadores , Proteína C-Reactiva , Enfermedad de la Arteria Coronaria , Ezetimiba , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Intervención Coronaria Percutánea , Humanos , Masculino , Estudios Retrospectivos , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Persona de Mediana Edad , Biomarcadores/sangre , Resultado del Tratamiento , Intervención Coronaria Percutánea/métodos , Ezetimiba/uso terapéutico , Quimioterapia Combinada , Anciano , Rosuvastatina Cálcica/uso terapéutico , Atorvastatina/uso terapéutico , LDL-Colesterol/sangre , Anticolesterolemiantes/uso terapéutico , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/diagnóstico