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Pharmacokinetics of aztreonam in infected patients
Abstract:
Pharmacokinetic parameters of aztreonam were determined in 22 patients with severe Gram-negative infections, treated with 0.5 or 1 g tid as an infusion of 30 min duration. Plasma concentrations were determined microbiologically. Most patients had various degrees of renal impairment and they showed a wide variety of age and body weight. The mean calculated volume of distribution was 17.31 or 260 ml/kg. The total plasma clearance correlated well with the creatinine clearance; the mean plasma clearance was 82 ml/min and the extrapolated extrarenal clearance was 9 ml/min. Actually measured half lives of aztreonam varied between 1 h 20 min, in a patient with normal renal function, and 9 h 40 min in a patient with severely impaired renal function. The results differ from predictions by other authors. Based on our results a dosage adjustment schedule for renal impairment is suggested.
Insights
Aztreonam pharmacokinetic parameters were studied in patients with Gram-negative infections and renal impairment. Dosage adjustments are suggested based on creatinine clearance to optimize aztreonam therapy.
Area of Science:
- Pharmacology
- Infectious Diseases
- Nephrology
Background:
- Severe Gram-negative infections require effective antibiotic therapy.
- Aztreonam is a key antibiotic for treating Gram-negative bacterial infections.
- Understanding aztreonam pharmacokinetics is crucial for dose optimization, especially in patients with renal impairment.
Purpose of the Study:
- To determine the pharmacokinetic parameters of aztreonam in patients with severe Gram-negative infections.
- To investigate the influence of renal impairment on aztreonam pharmacokinetics.
- To propose a dosage adjustment schedule for aztreonam in patients with varying degrees of renal function.
Main Methods:
- Pharmacokinetic parameters of aztreonam were determined in 22 patients.
- Patients received aztreonam intravenously (0.5 or 1 g tid).
- Plasma concentrations were measured microbiologically, and correlated with creatinine clearance.
Main Results:
- Aztreonam's volume of distribution averaged 17.31 or 260 ml/kg.
- Total plasma clearance strongly correlated with creatinine clearance (mean 82 ml/min).
- Aztreonam half-life varied significantly, from 1 hour 20 minutes to 9 hours 40 minutes, depending on renal function.
Conclusions:
- Observed aztreonam pharmacokinetic parameters differ from previous predictions.
- Renal impairment significantly impacts aztreonam half-life and clearance.
- A revised dosage adjustment schedule for aztreonam in renal impairment is proposed based on these findings.