PHARMACOLOGY OF 13-CIS-RETINOIC ACID IN HUMANS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 2069-2073
Abstract
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. [per os] 13-cis-retinoic acid starting at 0.5 mg/kg per day, escalating over 4 wk to a maximum dose of 8 mg/kg per day in divided doses. Although there was a linear correlation of plasma concentration with dose escalation, large interindividual variations in peak plasma concentrations were noted. At the maximum drug dose, the mean peak plasma concentration was 4 .times. 10-6 M. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 .times. 10-6 M. The drug was metabolized extensively to a metabolite, the concentrations of which exceeded parent 13-cis-retinoic acid concentrations with chronic dosing. Retinol concentrations were below the normal range.