A new test for evaluating nonsteroidal anti-inflammatory drugs in vitro: inhibition of prostaglandin E2 production in minced intestinal tissue.
A new method for evaluating the inhibitory effect of nonsteroidal anti-inflammatory drugs on prostaglandin E2 production is presented. Minced rat intestinal tissue was incubated with a nonsteroidal anti-inflammatory drug and homogenized. After centrifugation, prostaglandin E2 in the supernatant was measured by radioimmunoassay. The production of prostaglandin E2 was decreased by nonsteroidal anti-inflammatory drugs, in a concentration-dependent manner, the order of potency being diclofenac greater than loxoprofen greater than indomethacin greater than ibuprofen greater than TA-847 (imidazole derivative). Loxoprofen, a prodrug, inhibited the prostaglandin E2 production. In a classical enzyme assay with sheep seminal vesicle microsomal prostaglandin endoperoxide synthase, the order of inhibitory potency was TA-847 greater than diclofenac greater than indomethacin greater than ibuprofen. The inhibitory effect of loxoprofen was very weak. On the other hand, the potency order of these nonsteroidal anti-inflammatory drugs, with regard to their anti-inflammatory effect as determined in the rat carrageenin-induced paw edema model, was loxoprofen greater than indomethacin greater than diclofenac greater than ibuprofen greater than TA-847. The results of the new method with intestinal tissue showed thus a good correlation with the anti-inflammatory activity in vivo.
Futaki
N
N
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Hamasaka
Y
Y
Arai
I
I
Higuchi
S
S
Otomo
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep; D013270:Stomach / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone