Nonsteroidal anti-inflammatory drugs: an analysis of the relationship between laboratory animal and clinical doses, including species scaling.
The pharmacologic activity of nonsteroidal anti-inflammatory drugs (NSAID) has generally been studied in multiple tests. We examined four commonly used tests [i.e., the carrageenan edema test (CARR), the ultraviolet light-induced erythema test (UVE), the phenyl benzoquinone stretching test (PBQ), and the acetic acid stretching test (RWTH)] to determine by statistical criteria which was the best predictor of human clinical dose. We found that CARR greater than UVE greater than PBQ greater than RWTH. The CARR test, but not UVE or PBQ, showed dose proportionality between laboratory test dose and clinical dose. The RWTH test appeared to show proportionality, but the sample size was quite small. With proportionality, the scaling factor between test dose and human dose could be examined. Dose was found to scale as surface area for CARR. This relationship could not be generalized and thus each pharmacologic test must be examined individually for scaling behavior between the test and human doses.
Otterness
I G
IG
Central Research Division, Pfizer, Inc., Groton, CT 06340.
Gans
D J
DJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D016227:Benzoquinones; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004890:Erythema / Q000188:drug therapy; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011809:Quinones / Q000037:antagonists & inhibitors; D051381:Rats; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D011809:Quinones; C029322:phenylbenzoquinone; D002351:Carrageenan