Metformin And Omeprazole Interaction In Vivo Pharmacokinetics In Rats

Objective: To establish a sensitive and stable high-performance liquidchromatography determination of plasma concentrations of metformin and omeprazolein rats, and investigated the interaction of metformin and omeprazole in vivopharmacokinetics in rats.Methods: The determination of omeprazole plasma concentrations in rats: Itemployed a Hypersil BDS C18column (150mm×4.60mm,5μm.). The mobile phaseof: water (0.8%acetic acid+0.4%triethylamine)-acetonitrile74:26(v:v), The flowrate was set at1mL/min, column temperature was35℃, the ultravioletdetector wasoperated at302nm, the sample injection volume of20μL. The determination ofmetformin plasma concentrations in rats: It employed a Hypersil BDS C18column (150mm×4.60mm,5μm) at35℃. The mobile phase consisted of (A)10.0mmol/Ldipotassium hydrogen phosphate buffer+3.7mmol/L SDS (pH5.5)-(B) methy alcohol60:40(v:v). The flow rate was set at0.8mL/min and the ultravioletdetector wasoperated at236nm. Sample size set at20μL. Animal experiments: Group1isomeprazole monotherapy group, rats were gavaged omeprazole at4mg/kg, bloodsamples were collected at different time points after administration; Group2omeprazole and metformin hydrochloride combination group, rats were gavagedomeprazole at4mg/kg and metformin hydrochloride at150mg/kg, at different timepoints after administration, blood samples were collected; Group3metforminhydrochloride monotherapy group, rats were gavaged metformin hydrochloride at150mg/kg, blood samples were collected at different time points after administration; Group4after six days of continuous administration of omeprazole and metforminhydrochloride combination group, rats were gavaged with omeprazole at4mg/kg for6days, on the sixth day, the rats were gavaged metformin hydrochloride at150mg/kgand omeprazole at4mg/kg, blood samples were collected at different time points afteradministration. All plasma samples were process and analyse by HPLC,Pharmacokinetics with DAS2.0statistical software for automatic fitting process,calculate the pharmacokinetic parameters and curves for each group.Results: The linear range of omeprazole is from0.0500to4.00μg/mL. Theinner-day precision and intra-day precision were less than15%, and accuracy werewithin±10%. The chromatographic run time for each sample is14.0min. The linearrange of metformin hydrochloride is from0.400to10.0μg/mL, and inner-dayprecision and intra-day precision were less than10%, and accuracy were within±10%.The run time for each sample is16.5min. The pharmacokinetic parameters of Cmaxofgroup1and group2was3.25±0.38mg/L,3.48±0.19mg/L; Tmax=1±0h,0.9±0.2h; T1/2=1.99±0.63h,2.48±0.92h; AUC0~∞was9.19±1.91mg·h·L-1,9.62±0.75mg·h·L-1; The pharmacokinetic parameters of Cmaxof group3and group4was7.75±0.67mg/L,19.0±3.8mg/L; Tmax=3±0h,1±0h; T1/2=4.66±1.41h,7.15±3.31h;AUC0~∞was57.3±3.9mg·h·L-1,75.8±16.3mg·h·L-1.Conclusions: The HPLC method is sensitive and stable. It can be used for thedetermination of plasma drug concentration of omeprazole and metformin in rats, andapplied to the pharmacokinetic experiment. We discover that continuous administrationof omeprazole can increase the bioavailability of metformin in rats, and metformin hasno effect on the pharmacokinetics of omeprazole in rats.