Plasma levels of proglumetacin and its metabolites after intravenous or oral administration in the dog.
The absolute bioavailability of 1H-indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl 2-[4-[4-[[4-(benzoylamino)-1,5-dioxopentyl]oxy]propyl]-1- piperazinyl]-ethyl ester (+/-) (proglumetacin, CR 604) was studied in 12 dogs, in a triple cross-over experiment with single doses of i.v. proglumetacin diphosphate, oral proglumetacin diphosphate or oral proglumetacin dimaleate. Determined were proglumetacin, 2'-[4-(3-hydroxypropyl)-piperazin-1-yl]-ethyl-(1-p- chlorobenzoyl-5-methoxy-2-methylindol-3-yl)-acetic acid (CR 1015), indometacin and proglumide in plasma. Proglumetacin and CR 1015 were found in plasma only after the i.v. administration. Conversely indometacin and proglumide were found after all administration routes. The areas under the curve of indometacin and of proglumide did not differ significantly after the three treatments, as shown by the analysis of variance.
Setnikar
I
I
Rotta Research Laboratorium, Monza/Milano, Italy.
Arigoni
R
R
Chisté
R
R
Makovec
F
F
Revel
L
L
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D007210:Indoleacetic Acids / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D007213:Indomethacin / Q000097:blood; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011377:Proglumide / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011377:Proglumide; C019541:proglumetacin; D007213:Indomethacin