RT Journal Article
SR Electronic
T1 Effect of fat tissue volume on the distribution kinetics of biperiden as a function of age in rats.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 258
OP 263
VO 18
IS 2
A1 K Yokogawa
A1 E Nakashima
A1 F Ichimura
YR 1990
UL http://dmd.aspetjournals.org/content/18/2/258.abstract
AB The relationship between the volume of fat tissue and variations in the time course of plasma biperiden concentration in rats has been examined in three different groups (4-, 10-, and 50-week-old rats). The plasma concentrations at 24 hr after iv injection of 3.2 mg/kg varied between 0.8 ng/ml (4-week-old rats) and 5.0 ng/ml (50-week-old rats). The rank order of the steady state distribution volume of biperiden was: 50-week-old rats greater than 10-week-old rats greater than 4-week-old rats. The fat volume of the whole body, extracted from the dried carcass with ether, varied between 42 g/kg (4-week-old rats) and 167 g/kg (50-week-old rats). 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 = 0.987). The fat/plasma concentration ratios at 8 hr after the iv injection varied between 600 (4-week-old rats) and 200 (50-week-old rats), whereas the brain/plasma concentration ratios were identical to those at steady state among the three 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. Age-related changes in tissue and plasma concentrations are discussed in relation to the clinical usefulness of the blood level monitoring.