Effect of cyclosporine on colchicine secretion by a liver canalicular transporter studied in vivo

Kermit V Speeg, Alma L. Maldonado, Julie Liaci, Donna Muirhead

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Abstract

The multidrug resistance transport protein is a normal constituent of the liver canalicular membrane, although its function has not been defined in vivo. Colchicine, a multidrug resistance substrate, is eliminated mainly by the liver. Cyclosporine reverses multidrug resistance in vitro, presumably by inhibiting the multidrug resistance transporter. This study assesses biliary colchicine elimination and the effect of cyclosporine on this process. After cyclosporine administration biliary colchicine clearance decreased from 11.6 ± 0.8 to 2.2 ± 0.4 ml/min kg (p < 0.05), and the colchicine bile/plasma ratio decreased from 166 ± 9 to 38 ± 5 (p < 0.05). Cremophor EL (a cyclosporine vehicle) transiently inhibited biliary colchicine clearance and colchicine bile/plasma ratio, but to a much smaller extent than cyclosporine in vehicle. Biliary cyclosporine clearance was 0.122 and 0.024 ml/min · kg after bolus doses of 2 or 10 mg/kg intravenously, respectively. Cyclosporine bile/plasma ratio was 1.3 to 5.2. When cyclosporine was given 16 hr before colchicine infusion, biliary colchicine clearance decreased 39% (p < 0.05), and colchicine bile/plasma ratio decreased 51% (p < 0.05). Thus colchicine is actively secreted into bile and will be useful in the study of the multidrug transporter in vivo. Cyclosporine profoundly inhibits colchicine secretion into bile but is itself mainly metabolized rather than secreted. If competition for a common carrier is the basis for the interaction, then cyclosporine represents a drug that binds to but is not transported by the canalicular transporter.

Original languageEnglish (US)
Pages (from-to)899-903
Number of pages5
JournalHepatology
Volume15
Issue number5
StatePublished - May 1992

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Colchicine
Cyclosporine
Liver
Bile
Multiple Drug Resistance
P-Glycoproteins
Carrier Proteins

ASJC Scopus subject areas

  • Hepatology

Cite this

Effect of cyclosporine on colchicine secretion by a liver canalicular transporter studied in vivo. / Speeg, Kermit V; Maldonado, Alma L.; Liaci, Julie; Muirhead, Donna.

In: Hepatology, Vol. 15, No. 5, 05.1992, p. 899-903.

Research output: Contribution to journalArticle

Speeg, KV, Maldonado, AL, Liaci, J & Muirhead, D 1992, 'Effect of cyclosporine on colchicine secretion by a liver canalicular transporter studied in vivo', Hepatology, vol. 15, no. 5, pp. 899-903.
Speeg, Kermit V ; Maldonado, Alma L. ; Liaci, Julie ; Muirhead, Donna. / Effect of cyclosporine on colchicine secretion by a liver canalicular transporter studied in vivo. In: Hepatology. 1992 ; Vol. 15, No. 5. pp. 899-903.
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