Duration of activity of the acid, methyl ester and amide of an orally active platelet aggregation inhibitory prostanoid in the rat.
The prostanoid 3-oxa-4,5,6-trinor-3,7-inter-m-phenylene PGE1 (OI-PGE1) has been shown to be a more potent inhibitor of ADP-induced human platelet aggregation than PGE1. OI-PGE1 inhibits ex vivo ADP-induced platelet aggregation for 60 minutes after an oral dose of 20 mg/kg to rats. Present studies compare duration of ex vivo inhibition of ADP-induced platelet aggregation in the rat by OI-PGE1, its methyl ester and amide after administration by various routes. All oral (p.o.) and intraduodenal (i.d.) doses were 20 mg/kg and all intravenous (i.v.) doses were 1 mg/kg. OI-PGE1 and its methyl ester had the same duration of activity after i.v. (60 min.) and p.o. (60 min.) administration, however, the methyl ester, when administered i.d., had a longer duration of activity than the free acid i.d. (greater than 90 min. vs. 60 min.). OI-PGE1-amide had significantly longer duration than the acid or methyl ester after i.v. (greater than 120 min.), p.o. (greater than 240 min.) or i.d. (greater than 240 min.) administration. Present data suggest that in the rat (1) intestinal absorption of  OI-PGE1-methyl ester is more efficient than it is for the free acid and (2) due to metabolic and/or distributional differences between OI-PGE1 and its amide, the amide has a much greater duration of activity.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D004386:Duodenum; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage*; D051381:Rats
D011459:Prostaglandins E, Synthetic; D000244:Adenosine Diphosphate