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, biliary 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 calculated based on urinary excretion rates. Duodenal perfusion and marker 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 calculated by dividing the infusion rate by the plasma concentration. Biliary clearance 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). Total and renal clearance were diminished (total clearance: 121.4 +/- 21.6 ml/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 changed (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 recommend reduced dosage. On the contrary, it might even be necessary to increase the dose when treating biliary tract infections in patients with cholestasis in order to assure effective drug concentrations in the bile.
Hildebrandt
R
R
Frauenklinik und Poliklinik, Benjamin-Franklin-Klinikum, Freie Universität, Berlin, Germany.
Gundert-Remy
U
U
Raedsch
R
R
Sieg
A
A
Stiehl
A
A
D000328:Adult; D001646:Bile / Q000378:metabolism*; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008802:Mezlocillin / Q000378:metabolism / Q000493:pharmacokinetics*; D008875:Middle Aged; D010406:Penicillins / Q000378:metabolism / Q000493:pharmacokinetics*
D010406:Penicillins; D008802:Mezlocillin