Background : Orally administered all- trans -retinoic acid (all- trans -RA) can induce remission in a high proportion of patients with acute promyelocytic leukemia. Purpose : To further define the drug's pharmacokinetics, a study of intravenous all- trans -RA was per formed in rhesus monkeys. Methods : A total of nine monkeys received interavenous bolus injections of all- trans -RA. Three different doses(20, 50, and 100mg/m 2 ) were each tested in threee monkeys. Blood samples for determination of all- trans -RA concentration were obtained prior to drug administration and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 360 and 480 minutes after drug administration. Results : Plasma disapperance of all- trans -RA was charcterized by three distinct phases: a brief, intial exponential decline, followed by a relative plateau in the disappearance curve (the duration of which was dose dependent), and finally a terminal exponential decay. This profile is consistent with a capacity-limited (saturable) elimination process. The first order (terminal) half-life for all- trans RA averaged 19 minutes, and the mean clearances were 77, 52, and 59 mL/min for the 20, 50, and 100 mg/m 2 dose groups, respectively. The mean ± SD michaelis constant (K m ) for the Capacity-limited process was 3.2 ± 1.9 μM. Conclusions : Peak Plasma concentrations following oral admintratration of 45 mg/m 2 all-trans-RA in humans approach the k m for the capacity-limited process; thus, the dose-dependent pharmacokinetics of all- trans -RA described here may Occur within the clinically used occur within the clinically used dosage range. [J Natl Cancer Inst 84: 1332–1335, 1992]