Effects of hepatic function on vancomycin clinical pharmacology.
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.
D000328:Adult; D000368:Aged; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000502:physiology*; D008107:Liver Diseases / Q000378:metabolism; D008875:Middle Aged; D011817:Rabbits; D014640:Vancomycin / Q000378:metabolism*
D014640:Vancomycin; D003404:Creatinine