title: 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.
  
  
  OBJECTIVE
  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.
authors: Basilea Pharmaceutica International Ltd, Basel, Switzerland. anne.schmitt-hoffmann@basilea.com
authors: A H
authors: AH
authors: Schmitt-Hoffmann
authors: B
authors: B
authors: Roos
authors: J
authors: J
authors: Sauer
authors: M
authors: M
authors: Schleimer
authors: P
authors: P
authors: Kovācs
authors: K
authors: K
authors: Stoeckel
authors: J
authors: J
authors: Maares
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000077556:Alitretinoin; D001682:Biological Availability; D018592:Cross-Over Studies; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D000077556:Alitretinoin; D014212:Tretinoin