Pharmacokinetics of Prednisolone (PSL) during PSL Treatment

Pharmacokinetics of prednisolone (PSL) was investigated in 10 patients treated with long-term intermittent regimen of PSL administration, 4 consecutive days administration a week. In 8 patients (group I; 3 of nephrotic syndrome, 2 of SLE, and each of Crohn's disease, aortitis syndrome, and hemolytic anemia), PSL was initially administered daily until the therapeutic effects were achieved (daily period), and this was followed by consecutive 4 days administration (on-day) and consecutive 3 days discontinuation (off-day) of PSL every week (intermittent period), keeping the weekly dose of PSL in the preceding daily regimen. In 2 patients (group II) with multiple myeloma and idiopathic thromocytopenic purpura, respectively, PSL was started with the intermittent regimen of PSL without preceding daily period. In group I, pharmacokinetic studies by respective oral and i.v. administrations of 40mg PSL and of 25.6mg PSL hemisuccinate (equivalent to 20mg of PSL) were performed before treatment, in daily period and both on on-day and off-day within the same week during intermittent period. In one patient of group II, study only by intravenous PSL administration was performed before treatment and in intermittent period. In another patient of group II, studies by oral and intravenous PSL administration were performed only in an intermittent period. PSL was measured by radioimmunoassay. Paired t-test was used for the comparison. <BR>In each case of group I, there was no difference in Cmax, Tmax, or AUCp.o. after oral administration of PSL among 4 periods tested, before treatment, daily period, on-day and off-day during intermittent period. On the intravenous PSL administration, increase in AUCi.v., prolongation of half-life, and decreases in MCR and bioavailability on on-day of intermittent period were observed in comparison with those before treatment, respectively. Only bioavailability among these parameters on on-day was increased compared with that in daily period. On the other hand, on off-day of intermittent period, decrease in AUCi.v. and increase in MCR were observed compared with those on on-day within the same week. When each parameter on off-day was compared with that of daily period, decrease in AUCi.v. and increases in MCR and bioavailability on off-day were observed. Vd did not differ each other among these 4 periods. Remarkable finding was the fact that MCR fluctuated regularly in 4 periods of this therapy regimen, i.e., significant decrease in daily period compared with before treatment, no significant difference between on-day and daily period, and the increase on off-day compared with that on on-day or in daily period. Changes in MCR ob-served in intermittent period were independent on the duration or total dosage of PSL administered or the kind of disorders subjected. In group II, changes in AUCi.v. and MCR between on-day and off-day were similar to those in intermittent period in group I. <BR>Clinical side effects by PSL were rarely seen even during long-term administration of the intermittent PSL therapy, in which desired effects obtained with preceding daily PSL regimen were maintained. These findings suggest that MCR, which is widely accepted as one of the best index of pharmacokinetic parameter, fluctuates even within the same week during our intermittent PSL treatment with the decrease on on-day and increase on off-day, and that such a fluctuation repeats weekly throughout the period of a long-term intermittent therapy. The possibility was also suggested that such a fluctuation seems to be closely relevant to the maintenance of therapeutic effects and rare incidence of side effects during the PSL intermittent regimen.