ABSTRACT
The physiological approach to organ clearance is a simple approach that uses the organ’s ability to eliminate the drug, organ blood ¥ow, and protein binding to describe the rate of drug elimination by the organ and the drug prole in the body. This approach allows prediction of the change in drug disposition that occurs due to changes in organ blood ¥ow, enzymatic activity, and drug protein binding. For example, the hepatic clearance of a drug is dependent on the liver intrinsic ability to metabolize the drug, which is dependent on the enzyme activity, and the rate of delivery of the drug to the liver, which is dependent on the liver blood ¥ow. Enzyme induction and enzyme inhibition can alter the liver ability to metabolize the drug and can lead to changes in hepatic clearance. Also, diseases such as congestive heart failure and drugs such as beta-blockers can decrease the cardiac output and decrease the liver blood ¥ow, which may change the hepatic clearance of the drug.
