?????????????????????????????????????????о?

Pharmacokinetics Interaction between Valsartan and Nifedipine in Rats

??OBJECTIVE To establish an HPLC-UV method for the simultaneous determination of valsartan and nifedipine in rats plasma, so as to study the pharmacokinetic interaction between valsartan and nifedipine and to provide useful information for clinical practice. METHODS Eighteen male Wistar rats were divided into three groups: valsartan group(16 mg??kg^-1), nifedipine group (4.2 mg??kg^-1) and combined group (containing valsartan 16 mg??kg^-1, nifedipine 4.2 mg??kg^-1). Plasma samples were collected at 0, 0.08, 0.16, 0.25, 0.5, 0.75, 1, 2, 4, 8, 10, 24 h after the drug administration. An HPLC with UV detection method was developed to determine the concentration of valsartan and nifedipine in rat plasma, and the pharmacokinetic parameters were calculated using non-compartment model. RESULTS Compared with single valsartan group, the pharmacokinetic parameters ??_max and AUC_0-t of the combined group had a significant increase(P<0.05), while Tmax and CLz/F had a significant decrease(P<0.05). Compared with single nifedipine group, the pharmacokinetic parameters t_1/2z/h had a significant decrease(P<0.05), while other pharmacokinetic parameters had no significant differences. CONCLUSION Combination of valsartan and nifedipine could significantly improve the valsartan in rats plasma concentration and bioavailability, increase absorption and decrease excretion , while nifedipine shows no pharmacokinetic change in rats except shortened half-life.