Premium
Pharmacokinetics and Pharmacodynamics of 9‐cis‐Retinoic Acid in Healthy Men
Author(s) -
Weber Cornelia,
Dumont Etienne
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb04338.x
Subject(s) - pharmacokinetics , retinoic acid , pharmacodynamics , pharmacology , tolerability , placebo , metabolite , medicine , retinol , active metabolite , chemistry , tretinoin , area under the curve , endocrinology , adverse effect , biochemistry , vitamin , gene , alternative medicine , pathology
A double‐blind, placebo‐controlled, randomized study using single ascending oral doses of 5 mg, 15 mg, 40 mg, 80 mg, and 150 mg of 9‐cis‐retinoic acid was performed to assess the single‐dose pharmacokinetics, tolerability, and pharmacodynamic effects of 9‐cis‐retinoic acid in healthy men. Forty participants received treatment (six taking the active treatment and two taking placebo for each dose level). The pharmacokinetics of 9‐cis‐retinoic acid were linear over the dose range studied. Peak plasma concentrations were achieved within 3 to 4 hours on average. The half‐life was in the range of 1.3 to 2.4 hours. Metabolism was the major pathway of elimination. 4‐Oxo‐9‐cis‐retinoic acid, one of four metabolites measured, which included all‐trans‐retinoic acid and 13‐cis‐retinoic acid, was the main metabolite in plasma, achieving peak plasma levels of 41% to 83% of those of 9‐cis‐retinoic acid. Dose‐/concentration‐dependent reductions of retinol in plasma, with a maximum of 30% from baseline, were observed 24 hours after administration. Baseline levels were recovered after 5 days. Concentrations of retinol binding protein remained unchanged. Overall, the drug was well tolerated at all dose levels. Adverse events observed were consistent with findings of other retinoids (all‐trans‐retinoic acid and 13‐cis‐retinoic acid) and included headache and xeroderma at high dose levels.