Changes in prednisolone pharmacokinetics and protein binding during treatment with rifampicin.

Prednisolone pharmacokinetics and protein binding were studied after i.v. injection before and after three weeks of rifampicin therapy. The elimination half-time for prednisolone fell by 44.8% +/- 8.1% (p less than 0.01) and the area under the time-concentration curve by 47.5% +/- 7.3% (p less than 0.01). The reduction in area under the time concentration curve of free, non-protein bound prednisolone was 56.5% +/- 9.8% (p less than 0.01). The reduction in AUC was greater (p less than 0.05) for free prednisolone than for total prednisolone because of non-linear protein binding of prednisolone. The total body clearance of prednisolone increased from 73.5 +/- 14.6ml/min to 142.7 +/- 35.8ml/min (p less than 0.01). There was no change in the volume of distribution of prednisolone. Because of the marked reduction in the extent of bioavailability of total, and especially free, prednisolone, dosage adjustments should be made accordingly if prednisolone and rifampicin are prescribed concomitantly.