Changes in the pharmacokinetics of plasma total and free prednisolone during daily and intermittent regimens

To determine the pharmacokinetic changes of prednisolone associated with differing therapy regimens, we studied 15 patients with various diseases who were treated with daily doses of prednisolone and were then placed on an intermittent regimen, [administration for 4 consecutive days (on-day period), followed by 3 days cessation (off-day period)]. The mean duration of the study and the mean total dosage were 1.6 months and 2.4 g in the daily period, respectively, and 4.7 months and 3.5 g in the intermittent period, respectively. Blood was drawn for 6 h after iv administration of 20 mg prednisolone (average, 0.36 mg/kg). Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests were performed during the same week. The mean MCR of both total and free prednisolone decreased significantly in the daily and on-day periods compared with the pretreatment values. The decreased MCR during the on-day period was restored to the pretreatment level during the off-day period. A similar trend was observed in the changes in half-life, prolongation in the daily and on-day periods compared with the pretreatment value, and restoration to the pretreatment level during the off-day period. These alterations were not associated with the total duration or the total dosage of prednisolone administered. The results indicate that the pharmacokinetic parameters of prednisolone may periodically change during the intermittent regimen, and that off-day and on-day parameters are similar to those before therapy and during the daily period, respectively.