Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452.
OBJECTIVE
To examine the effect of food ingestion on the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, and the inhibitory effect on platelet aggregation.


METHODS
Fifty milligrams of S-1452 was given orally to eight healthy subjects with or without food. Blood samples for determinations of plasma drug concentrations and of its effects on platelet aggregation were taken for a 12-h post-drug period.


RESULTS
The maximum plasma concentration of S-1452 was reduced by 47% and the time to maximum concentration was prolonged from 0.5 to 1.9 h after dosing with food. The inhibitory effect of S-1452 on platelet aggregations induced by U-46619, a TXA2 receptor agonist, and collagen persisted up to 9 h after dosing with and without food. The degrees of inhibition in the two trials did not differ significantly at any point.


CONCLUSIONS
These results suggest that although the absorption of S-1452 is delayed and, consequently, its plasma concentration is decreased after dosing with food, the inhibitory effect on platelet aggregation is not significantly influenced after 50 mg of the drug.
Fujimura
A
A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Shiga
T
T
Kumagai
Y
Y
Ohashi
K
K
Ebihara
A
A
Kotegawa
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000328:Adult; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics* / Q000494:pharmacology; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000493:pharmacokinetics*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D011448:Prostaglandin Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C056566:S 145; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid