The Pharmacokinetics of Plasma Total and Free Prednisolone during an Alternate-day Regimen

Abstract

To determine the pharmacokinetic changes of prednisolone associated with an alternate-day regimen, 12 patients with various diseases were studied longitudinally. There were 9 patients (6 with systemic lupus erythematosus, 2 with sarcoidosis and one with polymyositis), who were treated with prednisolone (daily period) and subsequently put on an alternate-day regimen (alternate-day period). In 2 of the other patients (one with systemic lupus erythematosus and one with multiple sclerosis), the alternate-day regimen was preceded by the daily regimen, and subsequently an intermittent regimen consisting of 4 consecutive days on therapy and 3 days off therapy was followed. In the remaining patient with systemic lupus erythematosus, the treatment with the alternate-day regimen was initiated and followed throughout the treatment period. The mean duration and the mean total administered dose during the study were 1.1 months and 1.9 g in the daily period, and 7.8 months and 7.7 g in the alternate-day period. The test was done and blood was drawn for 6 hours after an intravenous administration of 20 mg prednisolone (0.36 mg/kg on the average) at the end of the respective regimen periods. In the daily period and the on-day of the alternate-day regimen, the pharmacokinetic study of iv prednisolone injection was done before the ingestion of oral prednisolone. The off-day test was done the next morning of the on-day. Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests in the alternate-day period were performed during the same week. The mean half life of both total and free prednisolone was prolonged significantly in the daily period and during the on-day and off-day of the alternate-day regimen compared with the pretreatment values. The mean metabolic clearance rates (MCR) of both total and free prednisolone decreased significantly in the daily period and during the on-day and off-day of the alternate-day period in comparison with the pretreatment values. No significant difference was found between either mean half life or MCR during the on-day and off-day of the alternate-day period. These findings were in contrast with our previously observed prednisolone pharmacokinetics during the intermittent regimen (4 days on therapy and 3 days off therapy within one week), in which pharmacokinetic parameters during the on-day (after 3 days of prednisolone ingestion) and off-day (after 3 off-days of prednisolone ingestion) periodically changed and were similar to those in the pre-treatment period and during the daily therapy period, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)