ABSTRACT
Background: Clozapine is an atypical antipsychotic drug that has been used world wide for the treatment of schizophrenic patients. Several generic formulations of this drug are now available.\ In order to assure about the efficacy and safety of the generic formulation, it is necessary to compare the bioavailability between the generic and the reference formulations after administration to the patients.Purpose: To compare the bioavailabilty of two clozapine formulations, Clozapin (Pharmasant Laboratories Co., Ltd., Thailand) and Clozaril (Novartis Pharmaceuticals, UK) when administered to schizophrenic patients in the dose of 100 mg every 12 hr until the drug reach steady state.Study design : Multiple dose steady state, randomized crossover study under non-fasting condition.\ The study was approved by the Ethics Review Board of the Khon Kaen University and the Food and Drug Administration, Ministry of Public Health.Subject : 18 Male Thai schizophrenic patients Methods: The subjects received 100 mg of either the Clozapin or Clozaril\ per oral bid for 7 days. At day 7 of each study phase, the drug levels were reached the steady state/\ Two hour after meal, the drug was administered and\ blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hr. Plasma was separated and stored at \–80oC until assay. The plasma concentration of clozapine was determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated from the plasma-concentration time profiles. The bioequivalence between the two formulations was assessed from the peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC0-12 ) ratios.\ Results: All subjects well tolerated both clozapine formulations. No serious adverse effects were reported. The Tmax, terminal half-life and the total plasma clearance of clozapine observed in the present study were comparable to those observed in other previous reports. All of the evaluated pharmacokinetic parameters between the Test and Reference formulations were of comparable. The 90% confident interval for the ratio of means for the LnCmax (0.9453-1.1182) and LnAUC0-12 (0.9734-1.0889) are within the guideline range of bioequivalence (0.80 to 1.25). Conclusion: The result demonstrated that the Test formulation, Clozapin was bioequivalent to the Reference formulation, Clozaril when orally administered in multiple \–dose to schizophrenic patients.
ABSTRACT
Background : Ceftazidime is a third generation cephalosporin that has been commercially available through several manufacturers and distributors in Thailand because of its widely clinical use. However, there is no bioequivalent study of this drug in Thais.\ The present study was conducted to compare the in vivo bioequivalent of ceftazidime obtained from an original (reference), and a local (tested) manufacturer in healthy Thai volunteers.Objective: To determine if two ceftazidime preparations (Fortum and Forzid) of different manufacturers are bioequivalent when administered intramuscularly.Design: Double-blind single-dose, two-period, randomized crossover study.Subjects: Fourteen Healthy Thai Volunteers.Methods and Interventions: Ceftazidime 1 g was administered intramuscularly to subjects. Blood samples were collected at predetermined intervals and assayed for ceftazidime concentration with HPLC. Pharmacokinetic parameters were calculated from the observed plasma-concentration time profiles. Maximum plasma concentration (Cmax), time to peak concentration (Tmax), areas under the concentration-time curve from 0 to 12 h (AUC0-12) and 0 to infinity (AUC0-) were the primary parameters considered in the determination of bioequivalence.Results: The two ceftazidime preparations were generally well tolerated by all volunteers. Administration of both preparations resulted in similar mean values for every pharmacokinetic parameters. Statistical analysis revealed no significant difference between the two preparations in any parameter, indicating that the two preparations are statistically bioequivalent (p\<0.05). The 90% confident interval (CI) for the ratio of the means for the Cmax (0.9281-1.1272) and AUC0- (0.9311-1.0184), are within the Food and Drug Administration Guideline range of bioequivalence (0.80 to 1.25).Conclusions: These results demonstrated that the tested ceftazidime preparation (Forzid) is bioequivalent to the reference ceftazidime preparation (Fortum) when administered intramuscularly.
ABSTRACT
Background: Sildenafil is a popular drug used for improving penile erectile function that has been commercially available through several manufacturers and distributors in Thailand. Therefore, it is necessary to study bioequivalence of the drugs obtained from the original manufacture and from a local manufacturer to ascertain that they can be medicated interchangeably.Objective: To determine whether two sildenafil preparations: Test (Erec®, Unison Laboratories, Co., Ltd., Thailand) and reference, (Viagra®, Pfizer Pty Limited., Australia) are bioequivalent.Design: Single oral dose and double-blind randomized two-way crossover.Population and samples: Fifteen healthy Thai male volunteers.Setting: Department of pharmacology, and Srinagarind Hospital, Faculty of Medicine, Khon Kaen University.Methods: The subjects received either 100 mg of the reference or test formulation. Blood samples were collected from catheter at several time points after sildenafil administration up to 12 hours. The bioequivalence between the two formulations was assessed by comparison of the peak plasma concentrations (Cmax) and area under the curve of time, from 0 to the last measurable concentration (AUC0-t last).Results: All subjects were well tolerated and presented no serious side effect. Statistical analysis revealed that the 90% confident intervals (CI) for the ratios between test and reference drugs of the log transformed the Cmax (0.8377-1.1985) and AUC0-t last (0.8610-1.1590), are within the Food and Drug Administration Guideline range of bioequivalence (0.80 to 1.25).Conclusions: It can be concluded that the 100 mg formulation of Test (Erec®) is bioequivalent to the Reference.Keywords: sildenafil, bioequivalence