A1 Refereed original research article in a scientific journal
Oral bioavailability of ospemifene improves with food intake
Authors: Koskimies P, Katila K, Lammintausta R, Aaltonen AM, Vuorinen J, Saarni O, Scheinin M
Publisher: DUSTRI-VERLAG DR KARL FEISTLE
Publication year: 2013
Journal: International Journal of Clinical Pharmacology and Therapeutics
Journal name in source: INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
Journal acronym: INT J CLIN PHARM TH
Number in series: 10
Volume: 51
Issue: 10
First page : 787
Last page: 794
Number of pages: 8
ISSN: 0946-1965
DOI: https://doi.org/10.5414/CP201873
Abstract
Objective: To assess the effect of concomitant food intake on the relative bio-availability 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 AUC(0-72h) and C-max 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: Food 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.
Objective: To assess the effect of concomitant food intake on the relative bio-availability 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 AUC(0-72h) and C-max 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: Food 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.
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