Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam.
Ampiroxicam is a nonacidic ether carbonate prodrug of piroxicam. Our results demonstrate that, in contrast to piroxicam, ampiroxicam does not possess detectable prostaglandin synthesis inhibitory activity in vitro. Ampiroxicam, however, has similar in vivo potency to piroxicam in suppressing paw swelling in rat adjuvant arthritis. In an acute model of paw inflammation in rats, ampiroxicam is less potent than piroxicam itself: the ED50's of ampiroxicam are 9- and 3.5-fold higher than those of piroxicam following a single or multiple (5) daily oral doses, respectively. Using the phenylbenzoquinone stretching test as a method of evaluating acute analgetic activity, the ED50 for ampiroxicam is about 3-fold higher than that of piroxicam. These tests of activity share the property of being partially prostaglandin-dependent. Ampiroxicam itself is not observed in plasma after oral dosing to man, nor in the rat, dog, and monkey as reported here. Bioavailability studies show that conversion to piroxicam is about 100%, 90%, 70%, and 50% in these four species, respectively. These results indicate that ampiroxicam's anti-inflammatory activity is produced in vivo by conversion to piroxicam and support its credentials as an efficacious prodrug of piroxicam.
Carty
T J
TJ
Department of Immunology and Infectious Disease, Pfizer Inc, Groton, CT 06340.
Marfat
A
A
Moore
P F
PF
Falkner
F C
FC
Twomey
T M
TM
Weissman
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D016227:Benzoquinones / Q000494:pharmacology; D001682:Biological Availability; D001711:Biotransformation; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D000882:Haplorhini; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000493:pharmacokinetics / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D011355:Prodrugs; D011448:Prostaglandin Antagonists; D013843:Thiazines; C065946:ampiroxicam; C029322:phenylbenzoquinone; D000001:Calcimycin; D011451:Prostaglandin-Endoperoxide Synthases