Pharmacokinetics of N-(4-hydroxyphenyl)-all-trans-retinamide in rats

Abstract

The concentration of N-(4-hydroxyphenyl)-all-trans-retinamide (HPR) was determined in plasma and a variety of tissues from rats after an intravenous dose (5 mg/kg). The plasma concentration-time curve could be accurately described by a triexponential equation. The apparent volume of distribution of HPR was approximately 10-12 liter/kg and the terminal half-life was 12 hr. Metabolites of HPR were more abundant than intact drug in most tissues 24 hr after the iv dose. A 5-day excretion study with radiolabeled HPR revealed that less than 2% of a single iv dose (5 mg/kg) is excreted as unmetabolized HPR in urine and feces and that most of the radioactivity is eliminated in the feces. HPR was incompletely absorbed after an oral dose (10 mg/kg).