Drug Safety

, Volume 32, Issue 7, pp 561–578 | Cite as

Pharmacokinetic Changes of Psychotropic Drugs in Patients with Liver Disease

Implications for Dose Adaptation
  • Chantal Schlatter
  • Sabin S. Egger
  • Lydia Tchambaz
  • Stephan Krähenbühl
Review Article


Dose adjustment of psychotropic drugs in patients with liver cirrhosis may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. Psychotropic drugs (antiepileptics, antiparkinsonian drugs, psycholeptics such as antipsychotics, anxiolytics, sedatives and hypnosedatives, and psychoanaleptics such as antidepressants, psychostimulants and antidementia drugs) marketed in Switzerland in 2006 were therefore classified according to their hepatic extraction and/or bioavailability to predict their kinetic behaviour in patients with cirrhosis. The expected changes in hepatic metabolism predicted by pharmacokinetic properties were compared with the results from kinetic studies carried out in patients with liver disease. These studies were identified using MEDLINE searches.

Of the 116 psychotropic drugs available on the Swiss market by the year 2006, only 12 were predominantly eliminated through the kidney. For five substances, no Q0 value (the dose fraction metabolized or excreted extrarenally) could be determined because of lack of pharmacokinetic data. Of 99 drugs with predominant hepatic metabolism, 29.3% were categorized as high, 25.2% as intermediate and 38.4% as low extraction drugs, while seven substances could not be classified. Pharmacokinetic studies in patients with liver disease were available for 55 of these 99 drugs eliminated predominantly by the liver (Q0-value ≥ 0.5). Only a few kinetic studies in patients with liver disease were found for antipsychotics, antiparkinsonian drugs and antidepressants, except for selective serotonin reuptake inhibitors and some newer antidepressants. The expected changes in pharmacokinetics were generally in good agreement with the changes reported in pharmacokinetic studies. For 12 drugs, the observed changes in pharmacokinetics from clinical studies were different from the changes expected based on their classification. However, for low extraction drugs metabolized by cytochrome P450 isozymes, clearance may be reduced by up to 50%.

In conclusion, the classification of drugs according to their hepatic extraction and/or bioavailability is a useful tool for dose adjustment, if information from clinical studies is lacking. There is a gap in information about pharmacokinetic changes in patients with liver cirrhosis for a large number of centrally acting drugs. Kinetic studies for centrally acting drugs with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.


Liver Cirrhosis Psychotropic Drug Cabergoline Oxcarbazepine Hepatic Clearance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by a grant from the Swiss National Science Foundation to Professor Stephan Krähenbühl (310000-112483). ## None of the authors have any conflicts of interest that are directly relevant to the content of this review. The funding organisation had no influence on the study design, analysis and interpretation of data or writing of the review. The authors all contributed equally to this work.

Supplementary material

40264_2012_32070561_MOESM1_ESM.pdf (550 kb)
Supplementary material, approximately 563 KB.


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Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  • Chantal Schlatter
    • 1
  • Sabin S. Egger
    • 1
  • Lydia Tchambaz
    • 1
  • Stephan Krähenbühl
    • 1
  1. 1.Division of Clinical Pharmacology & ToxicologyUniversity HospitalBaselSwitzerland

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