Effect of fat tissue volume on the distribution kinetics of biperiden as a function of age in rats.
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.
Yokogawa
K
K
Hospital Pharmacy, Kanazawa University, Japan.
Nakashima
E
E
Ichimura
F
F
D000273:Adipose Tissue / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001712:Biperiden / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D008954:Models, Biological; D010880:Piperidines / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D001798:Blood Proteins; D010880:Piperidines; D001712:Biperiden