Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer.
13-cis-Retinoic acid (13-CRA) is a synthetic analog of vitamin A effective reversing preneoplastic lesions in both humans and animals. To study its physiochemical properties and disposition kinetics, we developed a rapid, sensitive, and precise high-performance liquid chromatography assay for 13-CRA in biological samples. This assay system resulted in a clear separation of 13-CRA from all-trans-retinoic acid and retinol and had a detection limit of 20 ng/ml plasma. Recovery was 89 +/- 6% (S.D.) at equivalent physiological concentrations with a precision of 8%. To study the disposition kinetics in humans, 13 patients received a p.o. bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the first day of 13-CRA administration, the mean time to peak plasma concentration was 222 +/- 102 min. Interpatient peak 13-CRA plasma concentrations were found to be variable, suggesting irregular gastrointestinal absorption. Beta-Phase t 1/2 was approximately 25 hr. The prolonged terminal-phase plasma half-life may represent biliary excretion and enterohepatic circulation.
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D015474:Isotretinoin; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D012016:Reference Values; D014212:Tretinoin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D014801:Vitamin A / Q000097:blood
D014801:Vitamin A; D014212:Tretinoin; D015474:Isotretinoin