Disposition of nafcillin in patients with cirrhosis and extrahepatic biliary obstruction

Nafcillin, a semisynthetic penicillin effective against penicillinase-producing staphylococci, is eliminated largely in man via the liver. This study assessed the effect of cirrhosis and extrahepatic biliary obstruction in man on the pharmacokinetics of nafcillin. The plasma clearance of nafcillin controls was 583 +/- 144.2 ml per min (mean +/- SD) and fell strikingly to 291 +/- 147.6 and 163 +/- 56.3 ml per min in patients with cirrhosis and extrahepatic obstruction, respectively (P less than 0.001). In the latter two groups nafcillin excreted in urine increased from about 30 to 50% of administered dose (P less than 0.02), suggesting that renal disease superimposed on hepatic disease would further decrease over-all nafcillin clearance. The depression of nafcillin clearance with hepatobiliary disease did not correlate with any conventional liver laboratory test. The initial volume of distribution of nafcillin (V1) was unaltered but at steady state (Vd()) there was a significant reduction in the distribution volume in the patients with liver disease. Accordingly, the impairment in drug elimination, as assessed by its clearance from plasma, was underestimated by the prolongation of the nafcillin elimination half-life (t1/2(beta)) which was 1.02 +/- 0.20 hr in controls, and 1.23 +/- 0.31 (P greater than 0.05) and 1.73 +/- 0.44 hr (P less than 0.03), respectively, in patients with cirrhosis and extrahepatic obstruction.