Liver disease may produce significant, albeit highly variable, effects on the pharmacokinetic behaviour of
antibiotics in serum.
Drug disposition may be altered through several pathophysiological mechanisms including reduced hepatobiliary clearance, and modifications in the volume of distribution induced by
albumin synthesis deficiency or
portal hypertension-related
ascites.
Antibacterial agents are not affected by potential alteration in hepatic first-pass effects. Only
liver cirrhosis-induced effects on serum pharmacokinetics of
antibiotics have been extensively studied, unlike those possibly produced by other forms of
liver disease. In
liver cirrhosis, pharmacokinetic alterations of nearly all
beta-lactam or
quinolone agents appear not to be marked enough to require dosage adjustment, provided that renal function stays normal. Adaptation in therapeutic schedule, however, is warranted for those drugs that are substantially cleared by the hepatobiliary system, namely
mezlocillin,
clindamycin,
erythromycin,
pefloxacin,
enoxacin, antituberculous agents or
nitroimidazole derivatives. Special caution should also be exercised when using
aminoglycosides or
vancomycin because of the wide interpatient variability of their pharmacokinetic disposition and their toxic potential. When renal function is impaired and there is an increased volume of distribution due to
ascites, as frequently observed in severe
liver insufficiency, the elimination half-life of most
antibiotics is markedly prolonged, resulting in potential side effects due to
drug accumulation. Accordingly, dosage adjustment applies to all drugs. In this regard, it should be remembered that delineating the dosage guidelines for a given
antibiotic on the basis of reported pharmacokinetic parameters in patients with
liver cirrhosis is awkward and probably of limited value. This pattern is ascribed to large interpatient variability in the active hepatic cell mass, the degree of
portal hypertension and the alteration of serum binding capacity. Furthermore, there is no way of predicting accurately the extent of
liver insufficiency in an individual patient. Dosage reduction is thus done empirically in most cases. Whenever possible, direct measurements of serum
antibiotic concentrations should be the reasonable approach to manage
antibiotic therapy in this kind of clinical condition.