An estimate of the number of hepatocyte donors required to provide reasonable estimates of human hepatic clearance from in vitro experiments.
Cryopreserved human hepatocytes in suspension were used to estimate in vivo hepatic clearances for six different drugs. In vitro intrinsic clearances were measured on the basis of substrate depletion. The number of different hepatocyte donors required for a reasonable estimate of in vivo hepatic clearance--within twice or (1/2) of the actual value--was determined. Depending upon the desired level of confidence, anywhere from 9-20 donors are required by this method.
Department of Pharmacology, The University of Toledo College of Pharmacy, 2801 W. Bancroft St., Toledo, OH 43606, USA.
James
J
Byers
Kenneth
K
Bachmann
Heather
H
Eng
Anand
A
Katta
Donald
D
White
Ritwik
R
Ghosh
Nicola J
NJ
Hewitt
Paul
P
Silber
Genfu
G
Chen
D015925:Cryopreservation; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014019:Tissue Donors
D004364:Pharmaceutical Preparations