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Amphotericin B dose optimization in children with malignant diseases.
Christa E Nath1, Andrew J McLachlan, Peter J Shaw
1Department of Biochemistry, The Children's Hospital at Westmead, Westmead, Australia. Christan@chw.edu.au
Chemotherapy
|February 21, 2007
Summary
Rational dosing guidelines for amphotericin B-deoxycholate (AmB) in children were developed. New weight-based AmB doses aim to optimize therapeutic concentrations while minimizing kidney toxicity, ensuring safer prophylactic use in pediatric patients.
Area of Science:
- Pediatric Pharmacology
- Mycology
- Nephrology
Background:
- Amphotericin B-deoxycholate (AmB) is a critical antifungal agent.
- Optimizing AmB dosing in children is essential for efficacy and safety.
- Renal toxicity is a significant concern with AmB therapy.
Purpose of the Study:
- To establish rational, weight-based dosing guidelines for AmB in pediatric patients.
- To identify target AmB steady-state trough concentrations (C(ss,trough)) associated with minimal renal adverse effects.
- To propose starting dose adjustments based on body weight for children.
Main Methods:
- Measured AmB C(ss,trough) and plasma creatinine concentrations (C(creat)) in 83 children receiving prophylactic AmB.
- Determined maximum tolerable AmB C(ss,trough) by assessing the probability of significant C(creat) increases.
- Utilized a concentration-targeting approach to define dose requirements.
Main Results:
- A target AmB C(ss,trough) range of 0.76-1.05 mg/l was identified with a low probability of renal adverse effects (p < 0.29).
- Children weighing 25-45 kg achieved target concentrations with a 1 mg/kg/day AmB dose.
- Dosing adjustments were proposed: higher doses (1.25-1.5 mg/kg/day) for lighter children (10-25 kg) and lower doses (0.75 mg/kg/day) for heavier children (45-55 kg).
Conclusions:
- Proposed weight-based dosing guidelines for AmB in children aim to optimize therapeutic drug exposure.
- These guidelines suggest specific dose adjustments to achieve target concentrations and mitigate nephrotoxicity.
- Individualization and prospective evaluation of these starting dose guidelines are recommended for pediatric patients.
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