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 bi...

Full description

Saved in:
Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1993, Vol.32 (6), p.434-436
Main Authors: SPEEG, K. V, MALDONADO, A. L
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Antineoplastic agents
Bile - metabolism
Biological and medical sciences
Biological Transport - drug effects
Cell Membrane - metabolism
Colchicine - blood
Colchicine - pharmacokinetics
Cyclosporine - pharmacology
Drug Interactions
General aspects
Liver - metabolism
Male
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00685886