KINETICS OF TISSUE DISTRIBUTION AND ELIMINATION OF RETINOID DRUGS IN THE RAT .1. ACITRETIN

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