Abstract: AIM: To investigate the bioequivalence between losartan potassium tablets (Hangzhou Minsheng Pharmaceutical Co. Ltd) and losartan potassium tablets (Hangzhou MSD)and the influence of CYP2C9^*3 polymorphism on the metabolism of losartan.METHODS: We genotyped CYP2C9^*3 (rs1057910 A>C) sites of Healthy Chinese Han subjects by direct sequencing of PCR products to identify the distribution of CYP2C9^*3 polymorphism. We enrolled 36 subjects in the trial, among which CYP2C9^*1^*1 (AA) genotype were 32 cases and CYP2C9^*1/^* (AC) genotype were 4 cases. This study was designed to be two formulations, two-period crossover, single, open single-center trial of oral administration, the dose of losartan potassium tablets was 1 (50 mg/tablet). We established an HPLC-MS-MS method for the simultaneous determination of losartan and its metabolite E-3174 in human plasma. The pharmacokinetic parameters were calculated by Non-compartmental model using DAS3.2.2 analysis software.RESULTS: The relative bioavailability of two preparations were(101.5±21.5)% (losartan) and (100.0±13.8) % (E-3174); Compared with the AA genotype, AUC_0-12, AUC_inf and C_max of losartan of the AC genotype subjects were higher, and there had a significant difference of AUC_0-12 and AUC_inf; AUC_0-48 and AUC_inf of E-3174 were lower. There had no significant gene-related difference of AUC_0-48 and AUC_inf.CONCLUSION: The two preparations are bioequivalent. The clinical dosage of losartan may not be adjusted based on genotype in spite of CYP2C9 gene 1075A>C mutation slowing down losartan metabolism.

Key words: losartan potassium, LC-MS, bioequivalence, CYP2C9 polymorphism, pharmacokinetics