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Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations
D E Zaske1, R J Cipolle, J C Rotschafer
1Department of Surgery, School of Medicine, St. Paul, Minnesota.
Abstract:
Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.
Insights
Amikacin dosing requires careful consideration due to significant interpatient variability in pharmacokinetics. Individualizing amikacin dosage regimens is crucial for achieving therapeutic drug concentrations and minimizing toxicity risks.
Area of Science:
- Pharmacology
- Infectious Diseases
- Nephrology
Background:
- Amikacin is a critical antibiotic for treating gram-negative infections.
- Understanding its pharmacokinetic variability is essential for effective treatment.
Purpose of the Study:
- To investigate amikacin pharmacokinetics and dosage requirements in patients with gram-negative infections.
- To assess the impact of renal function on amikacin dosing.
Main Methods:
- Studied 98 patients undergoing amikacin treatment.
- Analyzed pharmacokinetic parameters including half-life and required daily dosage.
- Monitored serum creatinine levels for potential toxicity.
Main Results:
- Observed wide interpatient variation in amikacin's kinetic parameters.
- Half-life varied significantly even in patients with normal renal function.
- Daily dosage requirements showed considerable range (1.25–57 mg/kg).
- Four patients (4%) experienced potential amikacin-associated renal toxicity.
- One patient developed overt ototoxicity.
Conclusions:
- Amikacin pharmacokinetics exhibit substantial interpatient variability.
- Individualized dosing regimens are necessary to achieve therapeutic amikacin serum concentrations.
- Close monitoring for amikacin-associated toxicity, including renal and ototoxicity, is recommended.