RESUMEN
To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60-90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30-60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.
Asunto(s)
Antifúngicos , Trasplante de Células Madre Hematopoyéticas , Triazoles , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración Oral , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , China , Pueblos del Este de Asia , Modelos Biológicos , Estudios Retrospectivos , Suspensiones , Triazoles/farmacocinética , Triazoles/administración & dosificaciónRESUMEN
Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients' clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia. Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice. Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect. Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD's maximal therapeutic response, there existed a hysteresis. WDD's effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats. Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.
RESUMEN
WHAT IS KNOWN AND OBJECTIVE: Posaconazole is the second-generation triazole antifungal agent with widespread clinical application. Posaconazole exposure is influenced by various factors such as drug interactions, disease state and diet, resulting in a high interindividual variability in many patients and failure to ensure therapeutic efficacy. Therefore, it is necessary to conduct individualized therapy on posaconazole to ensure the efficacy and safety of treatment. METHODS: Articles were identified through PubMed using the keywords such as "posaconazole," "therapeutic drug monitoring" and "Population pharmacokinetics" from 1 January 2001 to 30 April 2022. RESULTS AND DISCUSSION: In this paper, we review the individualized treatment studies of posaconazole from the three aspects of therapeutic drug monitoring, population pharmacokinetic study and Monte Carlo simulation to provide reference for in-depth individualized posaconazole dosing studies. WHAT IS NEW AND CONCLUSION: This review suggests that therapeutic drug monitoring should be performed in patients taking posaconazole to adjust the dosage and assess the efficacy and cost-effectiveness of posaconazole under different clinical conditions and different dosing regimens through Monte Carlo simulations. In the future, a more detailed delineation and comprehensive examination of posaconazole PPK for specific populations requires further study.