Pharmacological activity, blood and tissue levels of indomethacin after single oral administration of two long-acting forms in the rat.
The duration of pharmacological action in the rat (carrageenin edema inhibition) of a long-acting indomethacin form (Dolcidium PL) was compared to that of a reference long-acting indomethacin form after a single oral dose (3 mg/kg) considered as the ED50 value and compatible with clinical use. Kinetic comparison of both forms was achieved in the blood and at the level of the inflammatory site. There was an identical bioavailability, but the rate of indomethacin release from the test preparation was significantly slower than that of the reference form. Greater pharmacological potency and significantly longer duration of action were also demonstrated for the former, indicating that this novel formulation exhibited better sustained release characteristics than the reference form, and thus exerted an optimal pharmacological effect (over 24 hr). Since there is a high degree of correlation of clinical efficacy with potency in the rat foot edema test, better effectiveness of Dolcidium PL should be expected in man. The reduction in peak plasma level of indomethacin should improve its tolerability as well.
Paluszezak
D
D
Laboratoire de Pharmacologie, Faculté de Pharmacie, Lille, France.
Bianchi
A
A
Chaoui
A
A
Cazin
J C
JC
Cazin
M
M
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D007213:Indomethacin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D007213:Indomethacin