Estudo de bioequivalência da clozapina em pacientes psicóticos no estado de equilíbrio

• Autor(a) principal: Timoteo, Margareth de Oliveira
• Data de Publicação: 2006
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal Fluminense (RIUFF)
• Texto Completo: https://app.uff.br/riuff/handle/1/17255
• topic: Clozapina; Bioequivalência; Biodisponiblidade relativa; Estado de equilíbrio; MEDICINA; CIÊNCIAS MÉDICAS; Esquizofrenia; Equivalência terapêutica; Agentes antipsicóticos; Disponibilidade biológica; Fluconazol; Clozapine; Bioequivalence; Bioavailability; Steady-state; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA

INTRODUCTION:Clozapine is a dibenzodiazepine derivative, tricyclic, with potent antipsychotic properties. The drug has low affinity for D2 receptors and therefore, it does not produce significant typical extrapyramidal syndrome amongst the usual drugs of that category. It is known as an atypical neuroleptic. Clozapine has been effective in schizophrenic patients refractory or intolerant to classical antipsychotic therapy. PURPOSE: To compare the relative bioavailability of two Clozapine formulations - 100 mg tablet Leponex from Novartis Pharma AG, Stein, Switzerland - as a Reference formulation and 100 mg tablet Zolapin® from Synthon BV Nijmegen Holand - as a Test formulation, through alternative analytical method to assess the bioequivalence between both formulations. The present study was conducted under actual living conditions of schizophrenic male patients, virgins of clozapine therapy, using a steadystate, multiple-dose of both drugs, randomized crossover study design. METHODS: The subjects received 100 mg twice a day of either the Reference formulation or the Test formulation for 10 days. At day- 10 of each study phase, blood samples were collected at 0 h (prior drug administration), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 h after drug administration. Plasma was separated and stored at -20°C until assay performed. The plasma concentration of Clozapine was determined by high performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated from the observed plasma-concentration time profiles using a short-cut chemical extraction. The bioequivalence between the two formulations was assessed by calculating individual peak plasma concentrations (Cmax) and the area under the concentration-time curve (AUC0-12 h) ratios. RESULTS: All subjects were well tolerated both Clozapine formulations. No serious adverse effects were reported. All of the pharmacokinetic parameters calculated in the present study were quite similar either for the Test or the Reference formulation. The 90% confident interval for both the means ratio lnCmax (0.9677 0.9937) and lnAUC0-12h (0.9811 1.0029) were within the guidelines range of bioequivalence (0.80 to 1.25) accepted by international regulatory standards. CONCLUSION: The result demonstrated that the Test formulation (Zolapin®), was bioequivalent to the Reference formulation (Leponex®), when orally administered in schizophrenic patients, both in terms of the rate and extent of absorption, and must be exchangeable