Study of the pharmacokinetics of vancomycin in patients with impaired liver function

Abstract

Infections caused by methicillin-resistant Staphylococcus aureus pose a serious problem postoperatively. Patients with hepatic dysfunction can be considered to be more susceptible to infection. Since little is known about the effects of the severity of hepatic dysfunction on the pharmacokinetics of vancomycin, we studied the pharmacokinetics of vancomycin in preoperative patients with hepatic dysfunction, after the intravenous infusion of 500 mg. In patients with liver disease and normal renal function, an enhancement of renal clearance caused by a reduction in percent protein binding was canceled out by a reduction in non-renal clearance caused by liver dysfunction, resulting in liver disease having no effect on the total clearance of the drug. In patients with impaired liver and renal functions and/or obstructive jaundice, the unbound fraction of vancomycin increased, whereas the renal excretion of vancomycin was delayed. It should be noted that an excessive increase in blood vancomycin concentration may be brought about even with a conventional dose in patients with hepatic dysfunction.