A Multi-centric Bioequivalence Trial in Ph+ Chronic Myeloid Leukemia Patients to Assess Bioequivalence and Safety Evaluation of Generic Imatinib Mesylate 400 mg Tablets / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was designed to characterize the pharmacokinetic profile and to assess bioequivalence of the sponsor's test formulation (imatinib mesylate 400 mg tablets) with an innovator product (Gleevec 400 mg tablets, Novartis Pharmaceuticals) under fed conditions, in adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) stabilized on imatinib mesylate 400 mg. In addition, the aim of this study was to monitor the safety profile of investigational medicinal products (IMPs). MATERIALS AND METHODS: A multicenter, randomized, open label, two-period, crossover, single dose bioequivalence study was designed for conduct under fed conditions in 42 adult Ph+ CML patients already stabilized on imatinib 400 mg tablets. Pharmacokinetic parameters Tmax, Cmax, and AUC0-24 were calculated using a non-compartmental model on validated WinNonlin software. Validated SAS software was used for statistical evaluation of data. The safety profile of investigational products was monitored during the course of study by applying a clinical process for recording observed untoward effects postadministration of investigational products. RESULTS: The 90% confidence intervals for the test/reference mean ratios of the ln-transformed PK variables Cmax (99.0%) and AUC0-24 (99.2%) were within an acceptable range of 80%-125%, as per bioequivalence assumptions. Both formulations were well tolerated after oral administration of IMPs. CONCLUSION: The test product was found to be bioequivalent and safe, and thus can be used interchangeably in clinical practice.

Comparative analysis of the protective effects of melatonin and silymarin on lipid peroxidation and dyslipidemia in STZ-induced diabetic rats

Purpose of this study was to compare the potential protective effects of Melatonin and Silymarin on blood glucose, serum lipid profile, tissue MDA and tissue glutathione in streptozotocin [STZ] induced diabetic rats. Diabetes was induced in Wistar rats by administration of a single dose of streptozotocin [60 mg/kg, i.p.] injection. STZ treatment significantly increased the levels of blood glucose, serum total cholesterol [TCh], serum triglycerides [TG] and tissue malondialdehyde [MDA], a secondary product of lipid peroxidation. On the contrary high density lipoprotein [HDL] cholesterol and glutathione [GSH] content of liver and pancreas were markedly decreased in diabetic control rats, Administration of Melatonin [16 mg/kg] and Silymarin [25 mg/ kg] caused a significant decrease in blood glucose, serum triglycerides, total cholesterol and tissue MDA with significant increase in serum HDL-cholesterol and tissue GSH content of STZ induced diabetic rats when compared with diabetic control rats. Blood glucose, serum TCh, serum TG and tissue MDA lowering effect of Melatonin was greater than that of Silymarin. Melatonin was also found to be more potent than Silymarin in increasing HDL and GSH content. Based on our findings, it is possible to postulate that Melatonin at much lower concentration is more potent than Silymarin in controlling diabetes