UPTAKE OF RIFAMPICIN BY ISOLATED RAT-LIVER CELLS - INTERACTION WITH SULFOBROMOPHTHALEIN UPTAKE AND EVIDENCE FOR SEPARATE CARRIERS

The mechanism of rifampicin uptake and its relation with that of BSP were studied in isolated rat liver cells. The cells take up rifampicin by a saturable process independent of metabolic energy since antimycin A and potassium cyanide were without effect. The analysis of the uptake revealed two systems which both follow Michaelis-Menten kinetics: the first, with high affinity, displayed an apparent Km of 0.13 ± 0.08 mM and an apparent Vmax of 2.3 ± 1.2 nmoles/min/mg protein; the second, with much lower affinity, had an apparent Km of 1.02 ± 0.46 mM and a Vmax of 16.0 ± 5.9 nmoles/min/mg protein. Whereas rifampicin exhibited an apparently competitive inhibition on BSP uptake, the uptake of rifampicin was not inhibited by BSP. Moreover, no reciprocal counterflow was observed between these two drugs. These results suggest that rifampicin enters the liver cells by a carrier-mediated process independent of that previously reported for BSP uptake. It is concluded that several carriers are involved in the uptake of anionic drugs by rat liver cells. © 1979.