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Aminoglycoside dosages and nephrotoxicity: quantitative relationships.
Florent Rougier1, Michel Ducher, Michel Maurin
1UMR CNRS 5558-ADCAPT Service Pharmaceutique, Hôpital Antoine Charial, Francheville, France.
Clinical Pharmacokinetics
|May 13, 2003
Summary
Once-daily amikacin administration (ODA) may delay nephrotoxicity onset compared to twice-daily dosing (TDA), particularly for shorter treatment durations. However, the benefit of ODA for reducing amikacin nephrotoxicity is not established for prolonged treatments.
Area of Science:
- Pharmacology
- Nephrology
- Clinical Pharmacy
Background:
- Amikacin is an aminoglycoside antibiotic used to treat serious bacterial infections.
- Nephrotoxicity is a significant adverse effect associated with aminoglycoside therapy.
- Dosage regimens, including once-daily (ODA) and twice-daily administration (TDA), may influence amikacin's safety profile.
Purpose of the Study:
- To develop a predictive model for amikacin-induced nephrotoxicity.
- To investigate the relationship between cumulative amikacin serum concentration (AUC) and the probability of nephrotoxicity.
- To compare the nephrotoxic potential of ODA versus TDA regimens.
Main Methods:
- Retrospective study involving two groups of patients who developed nephrotoxicity.
- Group 1: Patients treated with ODA (n=13).
- Group 2: Patients treated with TDA (n=22).
Main Results:
- The developed model effectively illustrates the impact of dosage regimen on amikacin nephrotoxicity.
- Nephrotoxicity onset was delayed in the ODA group (p=0.01) compared to TDA for equivalent daily doses.
- Cumulative amikacin AUC at nephrotoxicity onset was higher in the ODA group (p=0.029).
- At 50% probability of nephrotoxicity, cumulative AUC was 2613 mg·h/L for ODA versus 1521 mg·h/L for TDA.
- ODA demonstrated a greater difference in nephrotoxicity reduction at a cumulative AUC of 2495 mg·h/L, suggesting benefit for short-term (<7 days) therapy.
Conclusions:
- The advantage of ODA in reducing nephrotoxicity compared to TDA is not definitively established for prolonged amikacin treatments.
- Clinical decisions regarding amikacin dosage regimens should balance expected efficacy with potential toxicity for individualized patient care.
- Further research may be needed to clarify the optimal use of ODA and TDA in different clinical scenarios.