BILIARY-EXCRETION OF MEZLOCILLIN IN PATIENTS WITH HEPATIC-DISEASE

In three patients with liver disease (2 patients with alcoholic liver cirrhosis and 1 patient with chronic cholangitis) total, renal, biliar y and metabolic clearance of the acylureidopenicillin mezlocillin was examined under steady state conditions. Mezlocillin was infused for 6 hours at a constant infusion rate of 10 mg/min. Renal clearance was ca lculated based on urinary excretion rates. Duodenal perfusion and mark er dilution technique was applied to determine biliary excretion rates of the drug. Clearances were estimated by dividing the excretion rate by the respective plasma concentration. Total clearance was calculate d by dividing the infusion rate by the plasma concentration. Biliary c learance was markedly reduced in the patients compared to the data of 8 healthy controls (0.65 +/- 0.33 ml/min vs 98.6 +/- 42.5 ml/min). Tot al and renal clearance were diminished (total clearance: 121.4 +/- 21. 6 m/min vs 286.5 +/- 54.6 ml/min, renal clearance, 65.4 +/- 1.0 ml/min vs 137.6 +/- 32.6 ml/min). In contrast, metabolic clearance was not c hanged (53.3 +/- 23.1 ml/min vs 50.3 +/- 24.2 ml/min). As mezlocillin is well tolerated and has a wide margin of safety we do not recommed r educed dosage. On the contrary, it might even be necessary to increase the dose when treating biliary tract infections in patients with chol estasis in order to assure effective drug concentrations in the bile.