Effect of Liver Disease on Pharmacokinetics

Accordingly, these estimates may include a component of extrahepatic nonrenal clearance. The factors that affect hepatic clearance include blood flow to the liver (Q), the fraction of drug not bound to plasma proteins (fu), and intrinsic clearance (CLint) (1, 2). Intrinsic clearance is simply the clearance that would be observed in the absence of blood flow and protein binding restrictions. As discussed in Lecture 2, hepatic clearance usually can be considered to be a first-order process. In those cases, intrinsic clearance represents the ratio of Vmax / Km , and this relationship has been used as the basis for correlating in vitro studies of drug metabolism with in vivo results (3). However, for phenytoin and several other drugs the Michaelis-Menten equation is needed to characterize intrinsic clearance.