Hepatic drug clearance of three model compounds in normal subjects and cancer patients

Abstract

Hepatic drug clearance (HDC) plays a fundamental role in the metabolism and disposition of xenobiotics. Numerous methods of assessing HDC have been proposed in an effort to elucidate the genetic and extra-genetic effects upon xenobiotic biotransformation. One such method incorporates the co-administration of three model compounds to assess three unique parameters of HDC; namely, hepatic blood flow, Phase I (microsomal-mediated oxidative) metabolism, and Phase II (synthesis/conjugation) reactions. Pharmacokinetic studies of indocyanine green, antipyrine, and lorazepam were undertaken to assess each HDC parameter, respectively. This method was utilized to define differences in HDC between normal, healthy, young males and an older group with cancer.