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INTRODUCTION: Patients with Parkinson's disease (PD) present a variety of oral disease that can be worsened by xerostomia and sialorrhea. The patients' physical limitations, for example rigidity and tremor, add to the difficulty of oral care by the general dental surgeon. The objective of the present review was to organize a list of evidence-based recommendations for the oral care of patients with PD. METHODS: A systematic review of the literature was carried out by specialists who selected the relevant papers and created a list of recommendations based upon the literature. RESULTS: Fourteen papers (data reported in 16 articles) were included in this review. Patients with PD had reduced quality of oral health and hygiene, and high prevalence of gingival recession, periodontal disease, dental calculus, tooth decay, tooth mobility and loss, drooling, xerostomia, dysphagia and temporomandibular disorders. Most studies offered class IV evidence, while one paper had class II evidence. CONCLUSION: Patients with PD present poor oral health with conditions that are mostly preventable.
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To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (Cmax ), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69-106.16) for Cmax, 97.44% (90% CI = 91.85-103.37%) for area under curve of plasma concentration until the last concentration observed (AUClast ) and 98.30% (90% CI = 92.48-104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC0-inf ). Since the 90% CI for AUClast , AUC0-inf and Cmax ratios were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.
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Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Zolpidem/sangue , Zolpidem/farmacocinética , Adulto , Disponibilidade Biológica , Brasil , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Comprimidos , Adulto Jovem , Zolpidem/químicaRESUMO
BACKGROUND AND OBJECTIVES: Nanotechnology may increase the speed of penetration into the skin. This study evaluated the efficacy, safety, and pharmacokinetics of a novel topical anesthetic nanocapsule formulation (2 g) containing 2.5% lidocaine and 2.5% prilocaine (nanorap-test formulation) compared to placebo (control formulation) in skin types I-III patients of both sexes submitted to the ablative fractional CO2 laser treatment. METHODS: The patients (n = 120) included in this double-blind, single-center, randomized trial, received topical application of 2 g of the test formulation (50 mg lidocaine + 50 mg prilocaine) and placebo on the forehead region. Efficacy was assessed as pain sensation in four quadrants of each side of the forehead using a visual analogue scale immediately (0 min) and at 30, 60, and 90 minutes after laser application compared to placebo. The safety and tolerability of the test product were evaluated based on the occurrence of systemic adverse events as well as the occurrence of immediate and late skin reactions. Pharmacokinetic evaluation was performed in plasma of eight patients using a validated LC-MS/MS method for drugs quantification. RESULTS: Nanorap induced a clinically significant reduction in the pain assessment at all evaluated times (57.2%, 41.6%, 38.6%, and 37.3% at 0, 30, 60, and 90 minutes after drug application, respectively. Mean values of Cmax were 14.20 and 5.36 ng/ml and tmax were 3.5 and 1.8 hour for lidocaine and prilocaine, respectively. No systemic adverse events were observed. CONCLUSION: The nanorap formulation demonstrated a clinically and statistically significant efficacy providing analgesia after the ablative fractional CO2 laser therapy in the investigated patients, when compared to placebo. The product also presented good safety and tolerability. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Anestésicos Locais/administração & dosagem , Lasers de Gás/efeitos adversos , Combinação Lidocaína e Prilocaína/administração & dosagem , Nanocápsulas , Dor Processual/prevenção & controle , Adolescente , Adulto , Idoso , Anestésicos Locais/farmacocinética , Anestésicos Locais/uso terapêutico , Método Duplo-Cego , Feminino , Testa , Humanos , Combinação Lidocaína e Prilocaína/farmacocinética , Combinação Lidocaína e Prilocaína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Medição da Dor , Dor Processual/diagnóstico , Dor Processual/etiologia , Adulto JovemRESUMO
BACKGROUND: Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs, such as antibiotics. The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass (RYGB) surgery is unknown. OBJECTIVES: The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of amoxicillin. METHODS: This study was performed as a randomized, open-label, single-dose clinical trial, with two periods of treatment, in which obese subjects (n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery. The amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS). RESULTS: After the surgery, the mean weight loss was 17.03 ± 5.51 kg, and mean body mass index (BMI) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m2. The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUC0-tlast) increased significantly (3.5-fold); the maximum plasma concentration (Cmax) increased 2.8-fold after the bariatric surgery. No correlation was found between amoxicillin absorption, BMI, and weight loss percentage. CONCLUSION: The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery. However, despite this increase, its exposure was lower than the values reported for non-obese volunteers. TRIAL REGISTRATION: Identifiers: NCT03588273.
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Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Derivação Gástrica , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Índice de Massa Corporal , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Riluzole is a benzothiazole anticonvulsant used in the treatment of patients with amyotrophic lateral sclerosis and it is being investigated for clinical use in patients with spinal cord injury. The present study evaluated the pharmacokinetics of riluzole in beagle dogs after oral dose administration. METHODS: The oral doses (1.5, 5, 15 and 50 mg/kg) of riluzole were administered to beagle dogs and blood samples were collected from 0 h to 24 h post drug administration. Riluzole was quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). RESULTS: The method was sensitive, precise, accurate and selective to riluzole quantification in plasma of beagle dogs. The pharmacokinetics following oral administration was linear from 1.5 to 15 mg/kg and the t1/2 was 2.16, 1.5, 1.8 and 3.0 h after oral administration of 1.5, 5.0, 15 and 50 mg/kg riluzole. CONCLUSION: The riluzole pharmacokinetics was linear up to 15 mg/kg and had a significantlyshorter t1/2 in beagle dogs than in humans.
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Riluzol/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida/métodos , Cães , Feminino , Masculino , Plasma/metabolismo , Riluzol/sangue , Riluzol/farmacologia , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Espectrometria de Massas em Tandem/métodosRESUMO
INTRODUCTION: Vaginal route is often used in topical antifungal formulations. Vaginal permeability assays are generally performed as in vitro tests. METHOD: An in vivo vaginal permeability assay was developed using female rabbits. Fenticonazole permeability was evaluated by assessing fenticonazole bioavailability in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Toxicity was monitored histopathologically after 8 consecutive days of antifungal treatment (20â¯mg/animal). RESULTS: The method of quantification was linear with a lower limit of quantification (LLOQ) of (0.1â¯ng/mL). The area-under-the-curves (AUC) of fenticonazole on day 1 and 8 of treatment were 280.3⯱â¯86.1â¯ng/mLâ¯∗â¯h and 805.7⯱â¯252.4â¯ng/mLâ¯∗â¯h, respectively. The calculated systemic bioavailability was 12.73%⯱â¯0.14%. No signs of toxicity were observed both macroscopically and histologically after 8â¯days fenticonazole treatment. DISCUSSION: The plasma levels of fenticonazole observed in rabbits are similar to that observed in human. Rabbit vagina may be a suitable model to evaluate vaginal antifungal formulations.
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Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Vagina/metabolismo , Administração Intravaginal , Animais , Antifúngicos/sangue , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida/métodos , Feminino , Imidazóis/sangue , Permeabilidade , Coelhos , Espectrometria de Massas em Tandem/métodosRESUMO
Systemic arterial hypertension is a major risk factor for cerebrovascular disease. Therefore, adequate control of blood pressure is of enormous importance. One of the many fixed-dose single-pill antihypertensive formulations available on the market is the combination of nebivolol and hydrochlorothiazide. The objective of this study was to develop two distinct high-performance liquid chromatography coupled to tandem mass spectrometry methods to simultaneously quantify nebivolol and hydrochlorothiazide in human plasma. The methods were employed in a bioequivalence study, the first assay involving a nebivolol fixed-dose single-pill formulation based on healthy Brazilian volunteers. Nebilet HCT™ (nebivolol 5 mg + hydrochlorothiazide 12.5 mg tablet, manufactured by Menarini) was the test formulation. The reference formulations were Nebilet™ (nebivolol 5 mg tablet, manufactured by Menarini) and Clorana™ (hydrochlorothiazide 25 mg tablet, manufactured by Sanofi). For both analytes, liquid-liquid extraction was employed for sample preparation and the chromatographic run time was 3.5 min. The limits of quantification validated were 0.02 ng/mL for nebivolol and 1 ng/mL for hydrochlorothiazide. Since the 90% CI for Cmax , AUC(0-last) and AUC(0-inf) individual test/reference ratios were within the 80-125% interval indicative of bioequivalence, it was concluded that Nebilet HCT™ is bioequivalent to Nebilet™ and Clorana™.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hidroclorotiazida/farmacocinética , Nebivolol/farmacocinética , Espectrometria de Massas em Tandem/métodos , Adulto , Área Sob a Curva , Calibragem , Cromatografia Líquida de Alta Pressão/normas , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Voluntários Saudáveis , Humanos , Hidroclorotiazida/sangue , Masculino , Pessoa de Meia-Idade , Nebivolol/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/normas , Equivalência Terapêutica , Tramadol/sangueRESUMO
A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption.
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Carnitina/sangue , Fármacos Neuroprotetores/sangue , Piracetam/sangue , Administração Oral , Adolescente , Adulto , Disponibilidade Biológica , Carnitina/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Piracetam/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray/métodos , Comprimidos , Espectrometria de Massas em Tandem/métodos , Adulto JovemRESUMO
UNLABELLED: Lodenafil carbonate is a new phosphodiesterase Type 5 (PDE5) inhibitor used in treatment of erectile dysfunction. OBJECTIVE: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of lodenafil carbonate after administering ascending (1 - 100 mg) single oral doses to healthy male volunteers (n = 33). METHODS: The study was an open label, dose-escalation, Phase I clinical trial involving the administration of single oral doses of lodenafil carbonate. Lodenafil carbonate was administered sequentially, escalating in single doses of 1 mg - 100 mg with a washout period of at least 1 week between each dose. The progression to the next dose was allowed after clinical and laboratory exams, Ambulatory Monitoring of Arterial Pressure (AMAP) without relevant clinical modifications and adverse events without clinical relevancy. Blood samples were collected at pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 h post-dosing. Plasma samples for measurement of lodenafil carbonate and lodenafil were analyzed by liquid chromatography coupled to tandem mass spectrometry. RESULTS: No serious adverse events were observed, and none of the subjects discontinued the study due to intolerance. The AMAP measurements, clinical and laboratory exams and ECG revealed no significant changes even at higher doses. Lodenafil carbonate was not detected in any samples, indicating that it acts as a prodrug. The mean lodenafil pharmacokinetic parameters for tmax and t1/2 were 1.6 ( ± 0.4) h and 3.3 ( ± 1.1) h, respectively. This study demonstrated that lodenafil carbonate was well tolerated and showed a good safety profile in healthy male volunteers.
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Carbonatos/efeitos adversos , Inibidores da Fosfodiesterase 5/efeitos adversos , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Adolescente , Adulto , Monitorização Ambulatorial da Pressão Arterial , Carbonatos/farmacocinética , Eletrocardiografia/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacocinética , Pirimidinas/farmacocinéticaRESUMO
A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 µm analytical column (4.6 × 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 µg/mL (r>0.99). The limit of quantification was 0.1 µg/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI=88.16-99.79%) for C(max,) 98.31% (90% CI=94.91-101.83%) for AUC(last) and 97.67% (90% CI=94.45-101.01%) for AUC(0-168 h). Since the 90% CI for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless 100mg tablet) formulation manufactured by Biolab Sanus Farmacêutica Ltda. is bioequivalent to the Oroxadin (100 mg tablet) formulation for both the rate and the extent of absorption.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácidos Fíbricos/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Adolescente , Adulto , Feminino , Ácidos Fíbricos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Adulto JovemRESUMO
OBJECTIVE: in this study we have assessed the renal and cardiac consequences of ligature-induced periodontitis in both normotensive and nitric oxide (NO)-deficient (L-NAME-treated) hypertensive rats. MATERIALS AND METHODS: oral L-NAME (or water) treatment was started two weeks prior to induction of periodontitis. Rats were sacrificed 3, 7 or 14 days after ligature placement, and alveolar bone loss was evaluated radiographically. Thiobarbituric reactive species (TBARS; a lipid peroxidation index), protein nitrotyrosine (NT; a marker of protein nitration) and myeloperoxidase activity (MPO; a neutrophil marker) were determined in the heart and kidney. RESULTS: in NO-deficient hypertensive rats, periodontitis-induced alveolar bone loss was significantly diminished. In addition, periodontitis-induced cardiac NT elevation was completely prevented by L-NAME treatment. On the other hand L-NAME treatment enhanced MPO production in both heart and kidneys of rats with periodontitis. No changes due to periodontitis were observed in cardiac or renal TBARS content. CONCLUSIONS: in addition to mediating alveolar bone loss, NO contributes to systemic effects of periodontitis in the heart and kidney.
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Sequestradores de Radicais Livres/antagonistas & inibidores , Hipertensão/metabolismo , Rim/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/antagonistas & inibidores , Periodontite/metabolismo , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/metabolismo , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/fisiologia , Periodontite/diagnóstico por imagem , Peroxidase/análise , Radiografia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Tirosina/análogos & derivados , Tirosina/análiseRESUMO
OBJECTIVE: To assess the comparative bioavailability of two formulations (250 mg/5 mL suspension) of cefuroxime axetil (CAS 64544-07-6), administered with food, in healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained for up to 12 h post dose. Plasma cefuroxime axetil concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reactions monitoring (MRM). From the cefuroxime axetil plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUClast and Cmax. RESULTS: The limit of quantification was 0.1 microg/mL for plasma cefuroxime axetil analysis. The geometric mean and 90% confidence interval CI of test/reference product percent ratios were: 106.1% (100.8%-111.8%) for Cmax, 109.4% (104.8%-114.2%) for AUClast. CONCLUSION: Since the 90% CI for AUClast and Cmax ratios were within the 80-125% interval proposed by the US FDA, it was concluded that cefuroxime axetil (test formulation, 250 mg/5 mL suspension) was bioequivalent to a reference formulation under fed conditions, for both the rate and extent of absorption.
Assuntos
Antibacterianos/farmacocinética , Cefuroxima/análogos & derivados , Pró-Fármacos/farmacocinética , Adolescente , Adulto , Antibacterianos/administração & dosagem , Área Sob a Curva , Cefuroxima/administração & dosagem , Cefuroxima/farmacocinética , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Feminino , Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Fármacos/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray , Suspensões , Espectrometria de Massas em Tandem , Equivalência Terapêutica , Adulto JovemRESUMO
A rapid, sensitive and specific LC-MS/MS method was developed and validated for quantifying chlordesmethyldiazepam (CDDZ or delorazepam), the active metabolite of cloxazolam, in human plasma. In the analytical assay, bromazepam (internal standard) and CDDZ were extracted using a liquid-liquid extraction (diethyl-ether/hexane, 80/20, v/v) procedure. The LC-MS/MS method on a RP-C18 column had an overall run time of 5.0 min and was linear (1/x weighted) over the range 0.5-50 ng/mL (R > 0.999). The between-run precision was 8.0% (1.5 ng/mL), 7.6% (9 ng/mL), 7.4% (40 ng/mL), and 10.9% at the low limit of quantification-LLOQ (0.500 ng/mL). The between-run accuracies were 0.1, -1.5, -2.7 and 8.7% for the above mentioned concentrations, respectively. All current bioanalytical method validation requirements (FDA and ANVISA) were achieved and it was applied to the bioequivalence study (Cloxazolam -- test, Eurofarma Lab. Ltda and Olcadil -- reference, Novartis Biociências S/A). The relative bioavailability between both formulations was assessed by calculating individual test/reference ratios for Cmax, AUClast and AUC0-inf. The pharmacokinetic profiles indicated bioequivalence since all ratios were as proposed by FDA and ANVISA.
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Benzodiazepinas/sangue , Benzodiazepinas/farmacocinética , Cromatografia Líquida/métodos , Nordazepam/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Humanos , Limite de Detecção , Nordazepam/sangue , Nordazepam/farmacocinética , Reprodutibilidade dos Testes , Equivalência TerapêuticaRESUMO
Nitric oxide synthase (NOS) inhibitors are largely used to evaluate the NO contribution to pulmonary allergy, but contrasting data have been reported. In this study, pharmacological, biochemical and pharmacokinetic assays were performed to compare the effects of acute and long-term treatment of BALB/C mice with the non-selective NOS inhibitor L-NAME in ovalbumin (OVA)-challenged mice. Acute L-NAME treatment (50 mg/kg, gavage) significantly reduced the eosinophil number in bronchoalveolar lavage fluid (BALF). The inducible NOS (iNOS) inhibitor aminoguanidine (20 mg/kg/day in the drinking water) also significantly reduced the eosinophil number in BALF. In contrast, 3-week L-NAME treatment (50 and 150 mg/kg/day in the drinking water) significantly increased the pulmonary eosinophil influx. The constitutive NOS (cNOS) activity in brain and lungs was reduced by both acute and 3-week L-NAME treatments. The pulmonary iNOS activity was reduced by acute L-NAME (or aminoguanidine), but unaffected by 3-week L-NAME treatment. Acute L-NAME (or aminoguanidine) treatment was more efficient to reduce the NOx- levels compared with 3-week L-NAME treatment. The pharmacokinetic study revealed that L-NAME is not bioavailable when given orally. After acute L-NAME intake, serum concentrations of the metabolite Nomega-nitro-L-arginine decreased from 30 min to 24 h. In the 3-week L-NAME treatment, the Nomega-nitro-L-arginine concentration was close to the detection limit. In conclusion, 3-week treatment with l-NAME yields low serum Nomega-nitro-L-arginine concentrations, causing preferential inhibition of cNOS activity. Therefore, eosinophil influx potentiation by 3-week L-NAME treatment may reflect removal of protective cNOS-derived NO, with no interference on the ongoing inflammation due to iNOS-derived NO.
Assuntos
Inibidores Enzimáticos/farmacologia , Eosinófilos/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Administração Oral , Animais , Disponibilidade Biológica , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Líquido da Lavagem Broncoalveolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacocinética , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacocinética , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , OvalbuminaRESUMO
OBJECTIVE: To assess the comparative bioavailability of two formulations (40 mg delayed-released [DR] tablet; test and reference) of pantoprazole (CAS 102625-70-7) in healthy volunteers of both sexes, with and without food. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval, in two groups, with and without food. Plasma samples were obtained for up to 24 h post dose. Plasma pantoprazole concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). From the pantoprazole plasma concentration vs. time curves, the pharmacokinetic parameters AUC(last) and C(max) were obtained, with and without food. RESULTS: The limit of quantification was 5 ng/mL for plasma pantoprazole analysis. The geometric mean and 90% confidence interval CI of test/reference percent ratios were, without and with food, respectively: 104.6540% (90.8616%-120.5401%) and 99.9708% (90.9987%-109.8275%) for C(max), 95.6634% (85.2675%-107.3267%) and 89.3500% (83.6630%-95.4237%) for AUC(last). CONCLUSION: Since the 90% CI for AUC(last) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that pantoprazole 40 mg DR tablet (test formulation) with and without food was bioequivalent to the reference 40 mg DR tablet for both the rate and extent of absorption.
Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Estudos Cross-Over , Preparações de Ação Retardada , Jejum/metabolismo , Feminino , Interações Alimento-Droga , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol , Reprodutibilidade dos TestesRESUMO
A principal causa da gengivite é o acúmulo de placa bacteriana que pode ser evitada com a utilização de meios preventivos mecânicos e químicos. A clorexidina é um agente químico de amplo espectro antibacteriano. O objetivo do estudo foi a avaliação dos efeitos clínicos da clorexidina na saúde gengival, por meio de sua ação antibacteriana no controle da gengivite, em pacientes que apresentam pouca higienização da cavidade bucal no Distrito de São Carlos - Porto Velho RO. Através do Projeto NAPRA (Núcleo de Apoio a População Ribeirinhada Amazônia) foram selecionados 15 voluntários com gengivite, que foram divididos em grupo controle (cinco voluntários) e grupo clorexidina (10 voluntários). Para o grupo clorexidina foi administrado fármaco a base de clorexidina (Periogard® Colgate) e ao grupo controle foi administrado placebo (água). Os grupos foram monitorados a cada cinco dias, através de exames físicos e Índice Gengival de Lõe, durante um período de 15 dias. Antes do início do estudo, tanto o grupo estudo como o grupo controle encontravam-se equilibrados estatisticamente quanto à média de Índice Gengival de Lõe. Foi observado que o uso de clorexidina por um periodo de 10 dias reduziu e controlou significantemente a gengivite em pacientes que apresentavam higiene bucal deficiente, através de sua ação antibacteriana.
Assuntos
Clorexidina , Gengivite , Índice PeriodontalRESUMO
OBJECTIVE: The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of amiodarone (CAS 19774-82-4) in healthy volunteers of both sexes, with and without food. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval, in two groups, with and without food. Plasma samples were obtained for up to 240 h post dose. Plasma amiodarone concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). From the amiodarone plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained, with and without food: AUC(last), AUC(inf), AUC(0-240h), AUC(0-72h) and C(max). RESULTS: The limit of quantification was 1 ng/mL for plasma amiodarone analysis. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 107.61 (92.73-124.89) and 100.6 (94.1-107.5) for C(max), 107.05 (95.88-119.51) and 100.2 (96.0-104.7) for AUC(last), 107.27 (95.78-120.15) and 100.8 (97.0-104.8) for AUC(0-72h), 106.76 (95.84-118.94) and 100.2 (96.0-104.7) for AUC(0-240h) and AUC(inf) 105.15 (94.18-117.41) and 100.7 (96.6-105.0). CONCLUSION: Since the 90% CI for AUC(0-72) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that the amiodarone 200 mg tablet (test formulation) with and without food was bioequivalent to the reference 200 mg tablet for both the rate and extent of absorption.
Assuntos
Amiodarona/administração & dosagem , Amiodarona/farmacocinética , Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacocinética , Adulto , Amiodarona/sangue , Antiarrítmicos/sangue , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida , Estudos Cross-Over , Feminino , Alimentos , Humanos , Absorção Intestinal , Masculino , Espectrometria de Massas por Ionização por Electrospray , Comprimidos , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max). RESULTS: The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf). CONCLUSION: Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.
Assuntos
Clorpropamida/administração & dosagem , Clorpropamida/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Clorpropamida/sangue , Cromatografia Líquida , Estudos Cross-Over , Feminino , Humanos , Hipoglicemiantes/sangue , Absorção Intestinal , Masculino , Espectrometria de Massas por Ionização por Electrospray , Comprimidos , Espectrometria de Massas em TandemRESUMO
We report microwave-assisted synthetic routes, the pharmacokinetic profile along with results from ulcerogenicity and mutagenicity studies of atenolol aspirinate, and an already described derivative, in which acetyl salicylic acid (aspirin) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t(1/2) = 7.6 min). The results showed that the rapid and complete hydrolysis generates atenolol salicylate, which assumes a conformation stabilized by two intramolecular H-bonds, avoiding its further hydrolysis to salicylic acid and atenolol.
Assuntos
Anti-Hipertensivos/farmacocinética , Aspirina/química , Atenolol/farmacocinética , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/metabolismo , Área Sob a Curva , Atenolol/química , Atenolol/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Meia-Vida , Humanos , Micro-Ondas , Modelos Moleculares , Testes de Mutagenicidade , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacocinéticaRESUMO
A rapid, sensitive and specific method for quantifying the aromatase inhibitor (anastrozole) in human plasma using dexchlorpheniramine as the internal standard (I.S.) is described herein. The analyte and the I.S. were extracted from 200 microl of human plasma by liquid-liquid extraction using a mixture of diethyl ether:dichloromethane (70:30, v/v) solution. Extracts were removed and dried in the organic phase then reconstituted with 200 microl of acetonitrile:water (50:50; v/v). The extracts were analyzed by high performance liquid chromatography coupled with photospray tandem mass spectrometry (HPLC-MS-MS). Chromatography was performed isocratically on a Genesis, C18 4 microm analytical column (100 mm x 2.1mm i.d.). The method had a chromatographic run time of 2.5 min and a linear calibration curve ranging from 0.05-10 ng ml(-1). The limit of quantification (LOQ) was 0.05 ng ml(-1). This HPLC-MS-MS procedure was used to assess pharmacokinetic studies.