Drug prescribing in hepatobiliary disease.

Liver disease in man is associated with a variety of pathophysiological processes which may influence the disposition of drugs in several ways. Interpretation of the observed pharmacokinetic changes in liver disease requires an understanding of the relationship between systemic drug clearance (Cls), volume of distribution (Vd) and the elimination half-life [t1/2(beta)], i.e. t1/2(beta) = 0.693 . Vd/Cls. Half-life will be a measure of the fluctuation in drug level one may expect with continued administration of a drug while clearance will determine the dose required to achieve a particular steady state level. Liver disease may affect clearance and volume of distribution and so produce changes in half-life; in addition, alterations in plasma binding of drugs may occur and so influence free (unbound) drug levels. It is also possible that the end organ response, particularly in the case of sedative drugs, may be affected by liver disease. Other factors such as age, nutrition, smoking, and concomitant drug therapy may also influence drug elimination in patients with liver disease. At the present time, caution should be exercised in prescribing drugs to patients with liver disease and the dose should be titrated to the clinical response. The development of liver 'function' tests using model or marker drugs may offer some help to the prescriber in the future and enable a less empirical approach.