PT  - JOURNAL ARTICLE
AU  - A Rane
AU  - G R Wilkinson
AU  - D G Shand
TI  - Prediction of hepatic extraction ratio from in vitro measurement of intrinsic clearance.
DP  - 1977 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 420--424
VI  - 200
IP  - 2
4099  - http://jpet.aspetjournals.org/content/200/2/420.short
4100  - http://jpet.aspetjournals.org/content/200/2/420.full
SO  - J Pharmacol Exp Ther1977 Feb 01; 200
AB  - Under first-order conditions the activity of the hepatic drug-metabolizing enzymes may be closely approximated by the ratio of the in vitro kinetic constants Vmax and Km, which in turn is equivalent to the intrinsic clearance of the drug. In theory, after appropriate consideration for liver weight, blood flow and rug binding in the blood, the intrinsic clearance may be used to predict the extraction ratio for the total organ. This hypothesis was tested by comparing the predicted ratio based on a perfusion-limited model of hepatic elimination with that determined directly in the isolated perfused rat liver. Good agreement was obtained between the predicted and observed hepatic extraction ratios for antipyrine, carbamazepine, hexobarbital, phenytoin, propranolol, alprenolol and lidocaine, which span the extraction ratio from less than 0.1 to greater than 0.9.