Abstract

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.