USEFULNESS OF THE PAIN-INDUCED FUNCTIONAL IMPAIRMENT MODEL TO RELATE PLASMA-LEVELS OF ANALGESICS TO THEIR EFFICACY IN RATS

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for ph armacokinetic/pharmacodynamic modelling. This model evaluates analgesi a by measuring motor impairment of the right limb after intra-articula r administration of uric acid. Time of contact with a rotating cylinde r is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, a nd we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impair ment either in rats without uric acid or in the dysfunction produced b y uric acid. The relation between naproxen plasma concentration and th e analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plas ma levels of naproxen did not change when caffeine was co-administered . The PIFIR model with blood sampling is a suitable method for pharmac okinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.