title: Oral bioavailability of ospemifene improves with food intake.
abstract: OBJECTIVE
  To assess the effect of concomitant food intake on the relative bioavailability of ospemifene and its main metabolite, 4-hydroxyospemifene, after single oral dosing.
  
  
  METHODS
  This was an open-label, randomized, balanced, two-treatment (fed vs. fasted), two-period, two-sequence cross-over study in 24 healthy male subjects. Single 60-mg doses of ospemifene were administered without food or with a high-fat, high-energy breakfast (860 kcal). In an extension study, a single 60-mg dose of ospemifene was given to 12 subjects with a low-fat, light breakfast (300 kcal). Additional information was acquired by determining tablet dissolution profiles in media which reflected fasted and fed intestinal conditions.
  
  
  RESULTS
  The AUC0-72 h and Cmax of ospemifene were 2.8- and 3.6-fold higher after a high-fat breakfast and 1.9- and 2.3-fold higher after a low-fat breakfast when compared with an overnight fast. The variability in both primary pharmacokinetic parameters was considerably reduced (by up to 50%) with a meal, indicating more consistent absorption of ospemifene with concomitant food intake. Dissolution in conditions simulating fed intestinal fluid (high bile acid concentration) was increased 3-fold compared with dissolution in simulated fasted intestinal fluid.
  
  
  CONCLUSIONS
  wood markedly enhanced the extent and predictability of ospemifene absorption. The increase in bioavailability was not linearly related with the fat content of the meal. In vitro dissolution results were consistent with these clinical observations. Administration with food enhances and standardizes the oral bioavailability of ospemifene. Thus, it is recommended that ospemifene tablets should be taken with food.
authors.forename: Pasi
authors.initials: P
authors.lastname: Koskimies
authors.forename: Kirsi
authors.initials: K
authors.lastname: Katila
authors.forename: Risto
authors.initials: R
authors.lastname: Lammintausta
authors.forename: Anne-Mari
authors.initials: AM
authors.lastname: Aaltonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Vuorinen
authors.forename: Outi
authors.initials: O
authors.lastname: Saarni
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D059305:Diet, High-Fat / Q000379:methods; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005502:Food; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D013607:Tablets / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C571818:4-hydroxyospemifene; D013607:Tablets; D013629:Tamoxifen; C119141:Ospemifene