Effects of hepatic function on vancomycin clinical pharmacology

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Abstract
By use of a recently developed radioimmunoassay, 15 vancomycin pharmacology studies were performed in cancer patients with bacterial infections. Vancomycin (500 mg) was infused i.v. for 30 min every 6 h for up to 7 days. The plasma disappearance curve was biphasic, with an initial half-life of < 30 min. The 2nd half-life (t1/2.beta.), not dose related, varied from 1.4-231 h among the patients. In 6 studies of patients with normal hepatic functions, the t1/2.beta. was 2.6 h; the rate of total clearance was 162 ml/min. Nine 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 3434 .mu.g .cntdot. h/ml. Thus, liver function influences vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment.