Abstract
Liver and kidney are the main organs involved in the elimination of drugs. Both have a metabolic and a direct excretory capacity, but liver is generally the main organ responsible for drug metabolism and also metabolite excretion. Direct biliary excretion occurs also, but is sometimes a futile pathway because of enterohepatic cycling (reabsorption). Because of a variety of processes involved in drug elimination by the liver, liver disease can affect the pharmacokinetics by several mechanisms, for instance, reduced metabolic enzyme activity (Frye et al. 2006), altered hepatic uptake or biliary excretion by transporters and more generally reduced liver blood flow (Verbeeck 2008). Major plasma proteins are synthesized by the liver and drug pharmacokinetics can be affected by decreased plasma protein binding. Liver disease can also affect other organs such as the kidney.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
REFERENCES AND FURTHER READING
Bruno R, Hille D, Riva A, Vivier N, Ten Bokkel-Huinink WW, Van-Oosterom AT, Kaye SB, Verweij J, Fossella FV, Valero V, Rigas JR, Seidman AD (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16:187–196
EMEA CHMP (2005) Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with impaired hepatic function, August 2005
FDA (USA) (2003). Guidance for industry: pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling, May 2003
Frye RF, Zgheib NK, Matzke GR, Chaves-Gnecco D, Rabinovitz M, Shaikh OS, Branch RA (2006) Liver disease selectively modulates cytochrome P450-mediated metabolism. Clin Pharmacol Ther 80:235–245
Raymond E, Boige V, Faivre S, Sanderink GJ, Rixe O, Vernillet L, Jacques C, Gatineau M, Ducreux M, Armand JP (2002) Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction. J Clin Oncol 20:4303–4312
Verbeeck RK (2008) Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol 64:1147–1161
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Sanderink, G. (2011). Special Populations: Hepatic Impairment. In: Vogel, H.G., Maas, J., Gebauer, A. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89891-7_9
Download citation
DOI: https://doi.org/10.1007/978-3-540-89891-7_9
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-89890-0
Online ISBN: 978-3-540-89891-7
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences