PHARMACOKINETICS OF 13-CIS-RETINOIC ACID IN PATIENTS WITH ADVANCED CANCER

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 2087-2091
Abstract
13-cis-Retinoic acid (13-CRA) is a synthetic analog of vitamin A effective in reversing preneoplastic lesions in humans. To study its physicochemical properties and disposition kinetics, a rapid, sensitive, and precise high-performance liquid chromatography assay was developed 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.degree. (SD) at equivalent physiological concentrations with a precision of 8.degree.. To study the disposition kinetics in humans, 13 patients received a p.o. [per os] bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the 1st day of 13-CRA administration, the mean time to peak plasma concentration was 222 .+-. 102 min. Interpatient peak 13-CRA plasma concentrations were variable, suggesting irregular gastrointestinal absorption. .beta.-Phase t1/2 [half-life] was 25 h. The prolonged terminal-phase plasma t1/2 may represent biliary excretion and enterohepatic circulation.