Use of canalicular membrane vesicles (CMVs) from rats, dogs, monkeys and humans to assess drug transport across the canalicular membrane

A novel application of a Ultrafree filter cartridge/centrifugation method was evaluated to determine uptake in canalicular membrane vesicles from SD rats, beagle dogs, cynomolgus monkeys and humans to assess biliary transport

A.D. Shilling; F. Azam; J. Kao; L. Leung

2005

Scholarcy highlights

  • A novel application of a Ultrafree filter cartridge/centrifugation method was evaluated to determine uptake in canalicular membrane vesicles from SD rats, beagle dogs, cynomolgus monkeys and humans to assess biliary transport
  • CMVs prepared from fresh livers of rats, dogs, monkeys and humans were characterized for enrichment, basolateral and Golgi contamination and orientation
  • Correlation of in vitro data with in vivo findings was achieved by determining the biliary clearance of E2-Gluc in rats after a single i.v. dose and with literature in vivo data for leukotriene C4
  • The lower uptake of LTC4 by human than rat CMVs may be attributed to a higher Km value for human than rat CMVs
  • A novel application of a Ultrafree filter cartridge/centrifugation method was developed to determine uptake in CMVs from different preclinical animal safety species and humans, and may represent a useful approach to study the mechanism of biliary excretion during drug discovery and development
  • There are no financial, personal or other conflicts of interest involving this manuscript

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