Pharmacology of 13-cis-retinoic acid in humans.
Vitamin A and its analogs (retinoids) have shown great promise for the chemoprevention of cancer as well as being a possible new class of chemotherapeutic agents. A Phase I and II trial of 13-cis-retinoic acid in advanced cancers was initiated, and the clinical pharmacology of the drug was studied. All patients received p.o. 13-cis-retinoic acid starting at 0.5 mg/kg/day, escalating over 4 weeks to a maximum dose of 8 mg/kg/day in divided doses. Although there was a linear correlation of plasma concentration with dose escalation, large inter-individual variations in peak plasma concentrations were noted. At the maximum drug dose, the mean peak plasma concentration was 4 X 10(-6) M. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 X 10(-6) M. The drug was metabolized extensively to a metabolite, the concentrations of which exceeding parent 13-cis-retinoic acid concentrations with chronic dosing. Retinol concentrations were below the normal range.
D000284:Administration, Oral; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D006801:Humans; D015474:Isotretinoin; D013997:Time Factors; D014212:Tretinoin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D014801:Vitamin A / Q000097:blood
D014801:Vitamin A; D014212:Tretinoin; D015474:Isotretinoin