Bioequivalence of Clozapine Tablet in Thai Schizophrenic Patients

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.

Anti-herpes Simplex Virus type 1 Activity of Crude Ethyl Acetate Extract Derived from Leaves of Clinacanthus nutans Lindau

Clinacanthus nutans Lindau (C. nutans) is a well-known medicinal plant used in Thai folklore medicine for treatment of herpes simplex virus (HSV) infection. To study the inhibitory activity of crude ethyl acetate extract of C. nutans against HSV type 1 strain F (HSV-1F), crude ethyl acetate extract of C. nutans was tested in vitro on the Vero cells by using plaque reduction assay. The results showed that crude extract did not exert cytotoxic effects against Vero cells at the concentration of 19 \μg/ml or below and the CC₅₀ was 76 \μg/ml. The viruses were mixed with C. nutans crude extract at the subtoxic concentration of 19 \μg/ml and adsorbed on Vero cells. The infected Vero cells were then incubated in medium containing with crude extract. The results revealed that C. nutans crude extract completely (100%) inhibited the HSV-1F plaque formation and the IC₅₀ was 7.6 \μg/ml. To study the possible mode of antiviral action of crude extract, the experiment was conducted separately on the pre-or post-infection stage. In the pre-infection stage, crude extract produced 97% plaque reduction in a time-dependent manner, whereas it did not exert the inhibitory effect in the post-infection stages. This study suggested that the antiviral mode of action of crude ethyl acetate extract of C. nutans was effective greatly at the pre-infection stage, which may be due to the virucidal activity, inhibition of the viral attachment or the penetration. Therefore, there is still a clear need to further identify the possible mechanism of antiviral infection at the pre-infection stage of C. nutans crude extract at both the molecular and cellular levels.

Bioequivalence and Pharmacokinetic Study of Sildenafil in Healthy Thai Male Volunteers

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