title: Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment.
abstract: Although the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition, eventually culminating in end-stage liver disease that compromises hepatic drug metabolism. Consequently, the US Food and Drug Administration (FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range. A variety of noninvasive indices and radiologic procedures can be employed to assess hepatic drug metabolism and excretion. The Child-Pugh score is the most commonly used scale for assessing hepatic impairment among drugs submitted for US FDA approval. The score, originally developed to guide operative mortality in patients undergoing hepatic resection, has not been modified since its inception 5 decades ago. Furthermore, the score was not originally intended to be a guide for potential dose modification in patients with hepatic impairment. These reasons, in combination with the availability of a variety of new imaging modalities and an enhanced understanding of hepatic biology, should foster the development of novel methods to assess the effect of hepatic impairment on liver drug metabolism.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University at Buffalo, Buffalo, NY, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Talal
authors.affiliation: Center for Human Experimental Therapeutics, University of Rochester, Rochester, NY, USA.|AIDS Clinical Trials Group Pharmacology Specialty Laboratory, New York State Center of Excellence in Bioinformatics and Life Sciences; School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Venuto
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Islam
authors.initials: I
authors.lastname: Younis
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism*
keywords: cirrhosis; impaired hepatic function; liver drug metabolism; pharmacodynamics; pharmacokinetics