Kinetics of tissue distribution and elimination of retinoid drugs in the rat. I. Acitretin

EU Eisenhardt and MH Bickel

Department of Pharmacology, University of Berne, Switzerland.

Rats were injected with single intravenous doses of acitretin (6 mg/kg), and concentrations of the drug and its metabolite, 13-cis- acitretin, were determined in plasma and nine tissues up to 6 hr postdose. A newly developed sensitive method for the determination by HPLC of acitretin, 13-cis-acitretin, and etretinate was used. Acitretin rapidly appeared in liver and muscle, where it underwent redistribution into skin and adipose tissue. Tissue/plasma concentration ratios of acitretin ranged from 2.8 to 0.3 in the order adipose tissue > brain, liver > lung, heart, kidney, spleen > skin, muscle. Adipose tissue storage was moderate and short-lived. The metabolite, 13-cis-acitretin, was detected in all tissues but not in plasma; it accounted for < 10% of the administered dose at any time. No etretinate could be detected as a metabolite in plasma or tissues. After 6 hr, < 1% of the dose remained in the body as acitretin and 13-cis-acitretin. Disappearance was monophasic, with an elimination half-life of 70 min in plasma and 68 +/- 9 min in the nine tissues. The volume of distribution was 0.6 liters/kg and clearance 6 ml.min-1.kg-1. Acitretin was characterized by rapid first-order elimination and the absence of storage in a deep compartment.

Volume 22, Issue 1, pp. 26-30, 01/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics