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.
OBJECTIVE
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.


BACKGROUND
NCT02372344.
AstraZeneca KK.
Hitoshi
H
Shimada
AstraZeneca Gothenburg.
Catarina
C
Nilsson
AstraZeneca KK.
Yoshinori
Y
Noda
AstraZeneca KK.
Hyosung
H
Kim
AstraZeneca Gothenburg.
Torbjörn
T
Lundström
AstraZeneca KK.
Toshitaka
T
Yajima
D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004435:Eating; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005215:Fasting / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
D002264:Carboxylic Acids; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
Docosahexaenoic acid; Eicosapentaenoic acid; Japan; Omega-3 fatty acids; Pharmacokinetics