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- Title
Dose-Dependent Pharmacokinetics of All-trans-Retinoic Acid.
- Authors
Adamson, Peter C.; Balis, Frank M.; Smith, Malcom A.; Murphy, Robert F.; Godwin, Karen A.; Poplack, David G.
- Abstract
: Orally administered all--retinoic acid (all--RA) can induce remission in a high proportion of patients with acute promyelocytic leukemia. : To further define the drug's pharmacokinetics, a study of intravenous all--RA was per formed in rhesus monkeys. : A total of nine monkeys received interavenous bolus injections of all--RA. Three different doses(20, 50, and 100mg/m) were each tested in threee monkeys. Blood samples for determination of all--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. : Plasma disapperance of all--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- RA averaged 19 minutes, and the mean clearances were 77, 52, and 59 mL/min for the 20, 50, and 100 mg/m dose groups, respectively. The mean ± SD michaelis constant (K) for the Capacity-limited process was 3.2 ± 1.9 μM. : Peak Plasma concentrations following oral admintratration of 45 mg/mall-trans-RA in humans approach the k for the capacity-limited process; thus, the dose-dependent pharmacokinetics of all--RA described here may Occur within the clinically used occur within the clinically used dosage range. [J Natl Cancer Inst 84: 1332–1335, 1992]
- Publication
JNCI: Journal of the National Cancer Institute, 1992, Vol 84, Issue 17, p1332
- ISSN
0027-8874
- Publication type
Article