Drug metabolism in liver disease: Implications for therapeutic drug monitoring

Abstract

Over the last decades, a bulk of evidence has accumulated on the effect of liver disease on drug metabolism. It has convincingly been demonstrated that liver disease is associated with a reduced metabolic capacity with respect to drugs undergoing oxidative biotransformation, whereas conjugation reactions, especially glucuronidation, seem less affected. Nevertheless, many data have been conflicting, and it has become increasingly clear that differences in patient selection and severity of disease can account for these. Further, more recent communications suggest that liver disease led to a differential alteration of the cytochrome P-450s with regard to protein content and activity. From a clinical point of view, these findings may have important implications. However, when treating liver patients, we still have no generally accepted model for dose predictions; the best approach should be empiric and based on the clinical response. In selected cases, monitoring of plasma drug concentrations and liver function is recommended.