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Influence of food on the pharmacokinetics of oral alitretinoin (9‐ cis retinoic acid)
Author(s) -
SchmittHoffmann A. H.,
Roos B.,
Sauer J.,
Schleimer M.,
Kovācs P.,
Stoeckel K.,
Maares J.
Publication year - 2011
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2011.04033.x
Subject(s) - crossover study , pharmacokinetics , bioavailability , medicine , oral administration , dosing , concomitant , area under the curve , adverse effect , coefficient of variation , pharmacology , chemistry , alternative medicine , pathology , chromatography , placebo
Summary 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.