Effects of hepatic function on vancomycin clinical pharmacology

Antimicrob Agents Chemother. 1983 Apr;23(4):603-9. doi: 10.1128/AAC.23.4.603.

Abstract

Using a recently developed radioimmunoassay, we performed 15 vancomycin pharmacology studies in cancer patients with infections. Vancomycin (500 mg) was infused intravenously for 30 min every 6 h for up to 7 days. The plasma disappearance curve was biphasic, with an initial half-life of less than 30 min. The second half-life (t1/2 beta), not dose related, varied from 1.4 to 231 h among the patients. In six studies of patients with normal hepatic functions, the t1/2 beta was 2.6 h; the rate of total clearance was 162 ml/min. In contrast, nine studies of patients with impaired liver function had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min. These factors resulted in an increase in the value of area under the concentration-time curve from 59 to 3,434 micrograms X h/ml. These results have demonstrated the importance of the effects of liver function on vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Creatinine / metabolism
  • Female
  • Humans
  • Kidney / metabolism
  • Kinetics
  • Liver / physiology*
  • Liver Diseases / metabolism
  • Middle Aged
  • Rabbits
  • Vancomycin / metabolism*

Substances

  • Vancomycin
  • Creatinine