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Analysis of hepatic transport of cefpiramide in rats with obstructive jaundice by using isolated hepatocytes
T Yamao1, S Nakayama, Y Kurosaki
1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Abstract:
The mechanism of the diminished biliary clearance of cefpiramide (CPM) in rats with obstructive jaundice (OJ) was investigated by using isolated hepatocytes. The kinetics of CPM uptake by hepatocytes isolated from normal rats and rats with OJ could be explained by the combination of saturable carrier-mediated and nonsaturable first-order rate processes. The maximum uptake rate (Vmax) of the carrier-mediated process was significantly decreased in OJ, compared with normal hepatocytes, while the Michaelis constant (Km) and the first-order rate constant (kd) were not significantly different. This result indicated that the number of CPM transport carriers was decreased in OJ hepatocytes. Further, no CPM uptake occurred from the serum of OJ rats into normal hepatocytes. Partial recovery of CPM uptake after treatment of OJ serum with activated charcoal suggested the accumulation of inhibitors of CPM uptake in OJ serum.