Evaluation of rat intestinal absorption data and correlation with human intestinal absorption.
The absorption of 111 drug and drug-like compounds was evaluated from 111 references based on the ratio of urinary excretion of drugs following oral and intravenous administration to intact rats and biliary excretion of bile duct-cannulated rats. Ninety-eight drug compounds for which both human and rat absorption data were available were selected for correlation analysis between the human and rat absorption. The result shows that the extent of absorption in these two species is similar. For 94% of the drugs the absorption difference between humans and rats is less than 20% and for 98% of drugs the difference is less than 30%. There is only one drug for which human absorption is significantly different from rat absorption. The standard deviation is 11% between human and rat absorption. The linear relationship between human and rat absorption forced through the origin, as determined by least squares regression, is %Absorption (human)=0.997%Absorption (rat) (n=98, SD=11). It is suggested that the absorption in rats could be used as an alternative method to human absorption in pre-clinical oral absorption studies.
Zhao
Yuan H
YH
Department of Chemistry, University College London, 20 Gordon Street, WC1H 0AJ, London, UK.
Abraham
Michael H
MH
Le
Joelle
J
Hersey
Anne
A
Luscombe
Chris N
CN
Beck
Gordon
G
Sherborne
Brad
B
Cooper
Ian
I
D000465:Algorithms; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D013045:Species Specificity
D004364:Pharmaceutical Preparations