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Mezlocillin kinetics in hepatic insufficiency
Clinical Pharmacology and Therapeutics
|January 1, 1983
Summary
Hepatic insufficiency significantly prolongs the elimination of mezlocillin, an antibiotic. This finding suggests a need for adjusted dosing guidelines in patients with liver dysfunction to ensure effective treatment.
Area of Science:
- Pharmacokinetics
- Hepatology
- Infectious Diseases
Background:
- Mezlocillin is an antibiotic commonly used for bacterial infections.
- Hepatic insufficiency can alter drug metabolism and elimination.
- Understanding mezlocillin's pharmacokinetic profile in liver disease is crucial for safe and effective therapy.
Purpose of the Study:
- To determine the elimination kinetics of mezlocillin in patients with hepatic insufficiency.
- To compare mezlocillin elimination in individuals with normal liver function versus those with hepatic insufficiency and normal renal function.
Main Methods:
- A single 3-gm intravenous dose of mezlocillin was administered to eight normal subjects and four patients with hepatic insufficiency.
- Patients with hepatic insufficiency had elevated serum bilirubin levels and prolonged prothrombin times, with normal creatinine clearances.
- Mezlocillin concentrations in serum were quantified using microbiologic assays, and kinetic analysis was performed using model-independent methods.
Main Results:
- The elimination half-life of mezlocillin was significantly longer in patients with hepatic insufficiency (2.62 hr) compared to normal subjects (0.96 hr).
- Mean total body clearance of mezlocillin was reduced in patients with hepatic insufficiency (125.4 ml/min) compared to normal subjects (247 ml/min).
Conclusions:
- Hepatic insufficiency markedly prolongs the elimination of mezlocillin.
- Altered mezlocillin pharmacokinetics in liver disease necessitate the establishment of revised therapeutic guidelines and potentially dose adjustments.