Dose adaptation of drugs in patients with liver disease

Abstract

In my thesis I defined strategies for dosage adaptation of drugs in patients with liver disease. The major goal of the thesis was to classify antineoplastic drugs and central nervous agents according to pharmacokinetic principles (hepatic extraction and bioavailability) and to provide recommendations for their use in patients with liver disease. The antineoplastic drugs and central nervous agents available on the market in Switzerland were therefore studied. In a second time a clinical study was planned in patients with liver cirrhosis to define methods of dose adaptation for high-extraction drugs. The dose adaptation of drugs in patients with liver disease is more difficult than in patients with renal disease. The dosage may have to be adjusted but the problem is to quantify the required changes. Ideally, there should be a predictive liver function test that allows a more precise dosing in patients with liver disease analogous to the creatinine clearance for patients with renal dysfunction. Unfortunately, no such practical system is available as yet. Despite the absence of such a test, kinetic parameters and clinical studies can both help determining the kinetic behavior of a drug and providing dosage adjustments.