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Human Plasma all-trans-, 13-cis- and 13-cis-4-Oxoretinoic Acid Profiles during Subchronic Vitamin A Supplementation: Comparison to Retinol and Retinyl Ester Plasma Levels^1,2,3,

Institut für Toxikologie und Embryonalpharmakologie, Freie Universität Berlin, Garystrasse 5, 1000 Berlin 33, Germany

Plasma concentrations of retinyl esters, retinol, retinol-binding protein and the polar retinol metabolites all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-4-oxoretinoic acid and 13-cis-4-oxoretinoic acid were measured for six male volunteers who received 0.46 mg retinyl palmitate per kilogram body weight as oily drops (equivalent to 0.25 mg retinol per kilogram body weight) once daily over a 20-d period. Retinol and retinol-binding protein levels remained virtually constant throughout the study. Following absorption of vitamin A, retinyl esters as well as all-trans-retinoic acid and 13-cis-retinoic acid were transiently increased in plasma. 13-cis-4-Oxoretinoic acid increased gradually to a steady state level present on d 10 or 20. All-trans-4-oxoretinoic acid was not detected in plasma of the volunteers, with the exception of one on d 10 of the study. Plasma pharmacokinetic profiles of retinyl esters and polar metabolites of retinol displayed great interindividual differences (peak concentrations, time to peak, area-under-the-concentration-time curve values) among the volunteers. Because of the relatively high and consistent steady state concentrations of plasma 13-cis-4-oxoretinoic acid, we suggest that this compound be further investigated as a biochemical marker of vitamin A uptake in humans.

KEY WORDS: • vitamin A • humans • retinol • retinyl ester • retinoic acid

¹ Supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 174, C 06).

² Parts of this work were presented at the 30th Meeting of the Teratology Society (USA), July 7–11, 1990, Victoria, BC, Canada [Eckhoff, C. & Nau, H. (1990) Identification and quantitation of 13-cis-retinoic acid and 13-cis-4-oxoretinoic acid in addition to all-trans-retinoic acid as metabolites of vitamin A in human plasma. Teratology, 41: 551 (abs. 86)].

³ The term vitamin A is used for dietary or supplemental retinol or retinyl esters.

⁴ On sabbatical leave from the Children's Hospital Research Foundation, Elland and Bethesda Avenues, Cincinnati, OH 45229-2899.

Manuscript received 27 July 1990. Revision accepted 26 November 1990.

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