Effect of cyclosporine on colchicine partitioning in the rat liver.

Colchicine is secreted into bile as a major pathway of elimination. Cyclosporine (CsA) inhibits colchicine biliary secretion. In the present study, the effects of cyclosporine and its vehicle (cremophor) on the partitioning of colchicine across the liver were studied. CsA decreased the colchicine bile/plasma ratio from 484 +/- 39 to 53 +/- 3 (P < 0.001). This effect was due to both a decrease in bile/liver partitioning (control, 35.1 +/- 1.2, vs CsA treatment, 9.2 +/- 0.5; p < 0.001) as well as a decrease in liver/plasma partitioning (control, 13.7 +/- 0.8, vs CsA treatment, 5.7 +/- 0.4; P < 0.001). Cremophor also decreased the colchicine bile/plasma ratio (317 +/- 19, P < 0.02 vs control), but this effect was due to a decrease in the liver/plasma ratio (9.99 +/- 0.7, P < 0.02 vs control) rather than the bile/liver ratio (31.9 +/- 2.1, P > 0.2 vs control). Inhibition at the canalicular membrane is consistent with the location of gp-170, the presumed transporter of colchicine.