Effect of treatment at night with S-1452, a thromboxane A2 receptor antagonist, on the morning rise in platelet aggregation.
It is well known that platelet aggregation shows a morning rise, which may contribute to the increase in the onset of ischaemic heart diseases during the morning period. The present study was undertaken to determine whether nocturnal dosage with S-1452, a thromboxane A2 receptor antagonist, would blunt the morning rise in platelet aggregability. S-1452 50 mg or placebo were given orally to 8 healthy subjects at 10.00 h (day trial) or 22.00 h (night trial) according to a cross-over design. Plasma concentrations of S-1452 and its metabolites, bisnor-(+)-S-145 and tetranor-(+)-S-145, and platelet aggregation were determined during the 12-hour period following the dose. Mean plasma concentrations of S-1452, bisnor-(+)-S-145 and tetranor-(+)-S-145 during the absorption phase were lower after the nocturnal dose than after the morning dose. The maximum plasma concentration and area under the plasma concentration-time curve of the compounds were also lower and the time to the maximum concentration were delayed after the treatment at night. A morning rise in platelet aggregation was observed following placebo treatment. The inhibitory effect of S-1452 on platelet aggregation was observed at 3 hours and persisted for up to 9 h in both trials. The results suggest that S-1452 is absorbed more slowly after the nocturnal dose than after the morning dose. However nocturnal treatment with 50 mg S-1452 may blunt the morning rise in platelet aggregability.
Fujimura
A
A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Kumagai
K
K
Ohashi
K
K
Ebihara
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000328:Adult; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010976:Platelet Count / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; C056566:S 145; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen