Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial
| Autor: | Catarina Nilsson, Toshitaka Yajima, Hyosung Kim, Torbjörn Lundström, Yoshinori Noda, Hitoshi Shimada |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Eicosapentaenoic acid Time Factors Carboxylic Acids 030204 cardiovascular system & hematology Eating chemistry.chemical_compound 0302 clinical medicine Japan 030212 general & internal medicine Omega-3 carboxylic acids chemistry.chemical_classification Meal Cross-Over Studies digestive oral and skin physiology Fasting Middle Aged Healthy Volunteers Docosahexaenoic acid Biochemistry Area Under Curve Original Article lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine Adult medicine.medical_specialty Docosahexaenoic Acids Biological Availability Young Adult 03 medical and health sciences Asian People Pharmacokinetics Internal medicine Fatty Acids Omega-3 Omega-3 fatty acids Internal Medicine medicine Humans business.industry Biochemistry (medical) Fatty acid Crossover study Bioavailability Endocrinology chemistry Dietary Supplements business |
| Zdroj: | Journal of Atherosclerosis and Thrombosis |
| ISSN: | 1880-3873 1340-3478 |
| Popis: | Aims: Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA. Methods: In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4 × 1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥ 10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA. Results: A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration–time curve from 0 to 72 h for EPA, DHA, and EPA + DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA + DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively. Conclusions: The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects. Trial registration: NCT02372344 |
| Databáze: | OpenAIRE |
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