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Influence of food on the pharmacokinetics of oral alitretinoin (9-cis retinoic acid).

Abstract：

BACKGROUND:Previous studies have shown that concomitant administration of food may enhance the bioavailability of oral retinoids. AIM:To assess the influence of food on the pharmacokinetics (PK) of alitretinoin after a single oral dose. METHODS:This was a single-dose, open-label, randomized, crossover study, which enrolled 30 healthy men, aged 18-44 years. Subjects received sequential doses of alitretinoin 40 mg either after fasting (treatment A) or 5 min after completion of a standard breakfast (treatment B), with the dosing sequence randomized (A/B or B/A). The washout period between the two doses was 1 week. Plasma concentrations over time were plotted and standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)) and elimination half-life (t(1/2)] were determined. RESULTS:Drug exposure was markedly increased when alitretinoin was taken with food compared with fasting, and there were significant increases in mean C(max) (82.8 vs.25.4 ng/mL, respectively) and AUC (220.2 vs. 55.7 ng · h/mL). The delaying effect of food on t(max) was less marked (median of 3.0 vs. 2.0 h). Administration with food also increased exposure to drug metabolites. Variability in exposure was markedly reduced if alitretinoin was taken with vs. without food (percentage coefficient of variation 40% vs. 74% for AUC; 49% vs. 85% for C(max)). Alitretinoin was generally well tolerated, with typical retinoid adverse reactions, mostly comprising headache. CONCLUSIONS:Intake of alitretinoin with food substantially increased the bioavailability of alitretinoin, but variability in exposure was reduced. Consequently, oral alitretinoin should be taken with food as outlined in the manufacturer's summary of product characteristics.

journal_name

Clin Exp Dermatol

journal_title

Clinical and experimental dermatology

authors

Schmitt-Hoffmann AH,Roos B,Sauer J,Schleimer M,Kovācs P,Stoeckel K,Maares J

doi

10.1111/j.1365-2230.2011.04033.x

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

18-23

eissn

0307-6938

issn

1365-2230

journal_volume

36 Suppl 2

pub_type

杂志文章,随机对照试验

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Influence of food on the pharmacokinetics of oral alitretinoin (9-cis retinoic acid).