Analysis of Fasting Effect on Biperiden Distribution Kinetics in Rats.

Analysis of fasting effect on biperiden distribution in rats was examined.The plasma concentration at 24 hr after i.v.injection of 3.2mg/kg varied between 0.45ng/ml (10-week-old fasted rats) and 1.4ng/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 2.3% was caused by fasting. There was a good correlation 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 8 hr 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.