INFLUENCE OF BIOCHEMICAL PARAMETERS OF LIVER-FUNCTION ON VANCOMYCIN PHARMACOKINETICS

The influence of biochemical parameters of hepatic function on vancomy cin pharmacokinetics was retrospectively evaluated in 76 adult patient s (age 18 to 81 pars), from biochemistry data gathered during routine therapeutic drug monitoring. All subjects had normal serum creatinine levels. Vancomycin concentrations were determined by fluorescence pola rization immunoassay in 101 paired serum samples. All data for vancomy cin concentration versus time were fitted to a one-compartment model u sing the bayesian approach. Bilirubin, transaminases (n=101), gamma-gl utamyl transferase (n=97), alkaline phosphatase (n=95), albumin (n=92) and lactate dehydrogenase (n=42) were determined. No strong correlati on was seen between any of the pharmacokinetic and biochemistry parame ters studied. In patients with hyperbilirubinaemia, the mean V-ss and t(1/2) were increased (V-ss: 0.75+/-0.31 versus 0.92+/-0.42 l . kg(-1) , p=0.020; t(1/2) 5.93+/-3.30 versus 7.48+/-4.44 hr, p=0.049). When li ver function was evaluated according to hepatic profile (normal, mildl y altered and severely altered), no significant differences were obser ved in vancomycin pharmacokinetics among the groups. In conclusion, va ncomycin pharmacokinetics are only weakly influenced by the biochemist ry parameters of liver function.