A study of the relationship between serum bile acids and propranolol pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in healthy controls.

The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of propranolol. An open-label crossover study was performed to determine the pharmacokinetics and pharmacodynamics of propranolol after oral (40 mg) and intravenous (1 mg) administration as well as the concentration of total and individual fasting serum bile acids in 15 patients with liver cirrhosis and 5 healthy controls.

Pharmacokinetic changes of psychotropic drugs in patients with liver disease: implications for dose adaptation.

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.