EFFECTS OF ACUTE AND CHRONIC INFLAMMATION ON THE PHARMACOKINETICS OF PREDNISOLONE IN RATS

The effects of acute and chronic stages of carrageenan-induced air-pou ch inflammation on the pharmacokinetics of prednisolone were studied i n male Wistar rats. Chronic inflammation produced a significant increa se in the area under the curve (AUC) of prednisolone compared to contr ol animals (6594 +/- 2144 vs 3530 +/- 2164 mu g.hr/ L). The effect of acute inflammation was not significant (AUC = 4996 +/- 3813). Both acu te and chronic inflammation also reduced the in vitro plasma protein b inding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 mu g.hr/L, compared to 1121 mu g.hr/L in the control group a nd 1823 mu g.hr/L after acute inflammation. The mean values of half-li fe and apparent volume of distribution at steady-state in each group w ere similar. These results indicate that prednisolone must be used wit h caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.