Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure.
OBJECTIVE
In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care.


METHODS
In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the beta-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg.l-1 for mezlocillin and 5 mg.l-1 for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n = 5) and/or sulbactam (n = 4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver.


RESULTS
The clearances by CVVHD (CLCVVHD) for mezlocillin ranged between 11.0 and 44.9 ml.min-1 and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CLCVVHD ranged between 10.1 and 22.8 ml.min-1 and serum half lives were 4.25-6.11 h, independent of liver function.


CONCLUSIONS
Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function.
Rohde
B
B
Department of Clinical Pharmacology, University of Rostock, Germany.
Werner
U
U
Hickstein
H
H
Ehmcke
H
H
Drewelow
B
B
D058186:Acute Kidney Injury / Q000628:therapy*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008802:Mezlocillin / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D010406:Penicillins / Q000097:blood / Q000493:pharmacokinetics*; D006435:Renal Dialysis / Q000379:methods*; D013407:Sulbactam / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D010406:Penicillins; D008802:Mezlocillin; D013407:Sulbactam