Abstract
The disposition characteristics of biperiden were investigated in rats, rabbits, beagles, and humans, and a physiologically based pharmacokinetic model was established by using the hepatic intrinsic clearance of unbound drug concentration and the tissue-to-plasma unbound concentration ratios. Protein-binding parameters and blood-to-plasma concentration ratios were determined, and linear parameters were obtained in beagles and humans over a wide concentration range. The hepatic intrinsic clearance of humans was predicted from the animal data. The coincidence of each tissue-to-plasma Unbound concentration ratio between rats and rabbits was confirmed in the steady state, and the mean tissue-to-plasma unbound concentration ratios were used for the prediction of the plasma concentration-time courses of beagles and humans. The predicted lines fitted the observed plasma concentrations of beagles and a patient well after a single intravenous injection and repeated intramuscular administrations, respectively.
| Original language | English |
|---|---|
| Pages (from-to) | 718-725 |
| Number of pages | 8 |
| Journal | Chemical and Pharmaceutical Bulletin |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1987 |
Keywords
- animal scale up
- beagle
- biperiden
- hepatic intrinsic clearance
- human
- physiological pharmacokinetics
- rabbit
- rat
- tissue-to-plasma unbound concentration ratio
ASJC Scopus subject areas
- Chemistry(all)
- Drug Discovery