絶食時のラットを用いたビペリデンの体内動態変動要因の解析

概要

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Analysis of fasting effect on biperiden distribution in rats was examined. The plasma concentration at 24hr after i. v. injection of 3.2 mg/kg varied between 0.4 ng/ml (10-week-old fasted rats) and 1.4 ng/ml (10-week-old normal rats). The steady state distribution volume of biperiden in the fasted rats was smaller by 2/3 than that in the normal rats. The determined percentage of fat tissue per body weight reduced from 7.6 to 2.35 was caused by fasting. There was a good cerrelation between the steady state distribution volume of biperiden per lean mass body weight and the fat volume per lean mass body weight (r=0.989) in four different groups (10-week-old fasted 4-, 10-, and 50-week-old normal rats). The fat/plasma concentration ratios at 8hr after the i. v. injection varied between 380 (10-week-old normal rats) and 550 (10-week-old fasted rats), whereas the brain/plasma concentration ratios were identical to those at steady state among the two groups. The time courses of biperiden concentration in plasma, brain, and fat were simulated using a physiological pharmacokinetic model. There was reasonable agreement between the model predictions and the observed data, suggesting that the change in the fat volume is a dominant determinant of the distribution volume of biperiden in rats. Changes in fasted tissue and plasma concentrations are discussed in relation to the clinical usefulness of the blood level monitoring.