A Physiologically Based Pharmacokinetic Model for Biperiden in Animals and Its Extrapolation to Humans

Emi Nakashima, Koichi Yokogawa, Fujio Ichimura, Tsukinaka Yamana, Kouichi Kurata, Hideki Kido, Nariyoshi Yamaguchi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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 languageEnglish
Pages (from-to)718-725
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Volume35
Issue number2
DOIs
Publication statusPublished - 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

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