Effects of acute and chronic inflammation on the pharmacokinetics of prednisolone in rats.

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 +/- 2144 vs 3530 +/- 2164 micrograms.hr/L). The effect of acute inflammation was not significant (AUC = 4996 +/- 3813). Both acute and chronic inflammation also reduced the in vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 micrograms.hr/L, compared to 1121 micrograms.hr/L in the control group and 1823 micrograms.hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.