The Studies On Bioequivalence Of Ibuprofen And Pseudoephedrine Dispersible Tablets And Ibuprofen Metabolism In Primarily Cultured Rat Hepatocytes

Objective: To study the Bioequivalence of Ibuprofen and pseudoephedrinedispersible tablets and Ibuprofen Metabolism in Primarily Cultured RatHepatocytes.Methods: l.In morning ,four tablets of test product (Ibuprofen and pseudoephedrine dispersible tablets, each tablet contains Ibuprofen 200mg pseudoephedrine hydrochloride 3Omg) or controlled product (Ibuprofen and pseudoephedrine tablets ) were given to 22 fasted healthy volunteers in a randomized study. Ibuprofen and pseudoephedrine hydrochloride concentration in plasma were determined by HPLC method and naproxen and para-nitroaniline were used as internal standards respectively. The pharmacokinetic parameters of Ibuprofen and pseudoephedrine hydrochloride were calculated by 3P97. 2.The metabolism of Ibuprofen in isolated rat hepatocytes was preliminary investigated. Hepatocytes were prepared from rats using two-step perfusion and collagenase digestion procedure. 2.5 u g/mK 5 u g/mK 20 U g/ml concentrations of ibuprofen were incubated with normal and injured hepatocytes.The tests were divided into normal hepatocytes group, CCU hepatocytes injured group and H2O2 hepatocytes injured group. 1ml Aliquots was withdrawn from the incubation mixture at different time points of incubation. The concentrations of Ibuprofen in hepatocyte suspension were determined by HPLC method.Results: 1 .On the plasma concentration-time curves of test product and controlled product , Ibuprofen and pseudoephedrine hydrochloride were fitted to the one compartment opened model with first-order absorption.The main pharmacokinetic parameters such as AUC(O-inf), AUC(O-t), Cp, Ti/2 had no significence (P>0.05) . The data of AUC and CP were log-transformed before anlalysis of variance , two sides t-testjustified bioequivalence.The statistical results showed two products had bioequivalence in vivo. 2.Compared with that of normal hepatocytes group, the main pharmacokinetic parameters of CCU hepatocytes injured group and H2O2 hepatocytes injured group which metalolized 2.5 ug/ml > 5 u g/ml > 20 u g/ml concentrations of Ibuprofen had signifence.At the same cell concentration, the lower the concentration of Ibuprofen, the fester the elimination is, and vice versaConclusion: 1. Affer 22 healthy volunteers orally taken test product and controlled product, the concentrations of Ibuprofen and pseudoephedrine hydrochloride were determined by HPLC method, the statistical results shows the test product is bioequivalent to the controlled product in vivo. 2. Pharmacokinetic parameters of injured groups have obvious changes, ti/2 delayed, AUC amplified, elimination decreased.