Pharmacokinetics of retinoids in women after meal consumption or vitamin A supplementation

• Published in: Journal of clinical pharmacology Vol. 36; no. 9; p. 799
• Main Authors: Chen, C, Mistry, G, Jensen, B, Heizmann, P, Timm, U, van Brummelen, P, Rakhit, A K
• Format: Journal Article
• Language: English
• Published: England 01.09.1996
• Subjects: Adult; Area Under Curve; Drug Interactions; Female; Food; Food Analysis; Food-Drug Interactions; Humans; Isotretinoin - pharmacokinetics; Keratolytic Agents - pharmacokinetics; Metabolic Clearance Rate; Retinoids - blood; Retinoids - pharmacokinetics; Tretinoin - pharmacokinetics; Vitamin A - administration & dosage; Vitamin A - analysis
• ISSN: 0091-2700
• DOI: 10.1002/j.1552-4604.1996.tb04253.x

These studies were conducted to evaluate the pharmacokinetics of several retinoids after meal consumption or vitamin A supplementation to establish a reference for future assessment of teratogenic risks of retinoid therapeutic agents. In the first study, 36 healthy young female volunteers consumed single meals containing vitamin A amounts ranging from 1,305 to 169,474 IU. In the second study, 24 other female volunteers took vitamin A supplements at a dose level of 5,000, 10,000, or 25,000 IU/day for 60 days. Plasma concentrations of tretinoin, isotretinoin, 4-oxo-tretinoin, and 4-oxo-isotretinoin in samples collected during the studies were analyzed using a high-performance liquid chromatography method with ultraviolet detection. Pharmacokinetic parameters for the retinoids were calculated using model-independent methods. Plasma concentrations of tretinoin were not altered by meal consumption or vitamin A supplementation. Plasma levels of 4-oxo-tretinoin were below the assay detection limit (0.3 ng/mL) in the majority of samples collected throughout the studies. Linear relationships between dose and maximum concentration (Cmax) and dose and area under the concentration-time curve (AUC) for isotretinoin and 4-oxo-isotretinoin were derived from data from the meal study. For the most bioavailable formulation used in the supplement study, daily ingestion of 5,000 IU of vitamin A caused increases of 141 +/- 53% and 171 +/- 77% from baseline in the 24-hour AUCs of isotretinoin and 4-oxo-isotretinoin, respectively. Dose-related increases in systemic exposure to retinoids were observed after ingestion of vitamin A by means of a meal or a supplement. Findings from these studies can be used as a basis for future safety evaluations of retinoid compounds.