Amphotericin B dose optimization in children with malignant diseases
| Autor: | Peter J. Shaw, Christa E. Nath, John W. Earl, John C. Coakley, Andrew J. McLachlan |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Antifungal Agents
Adolescent Plasma creatinine Microbial Sensitivity Tests Trough (economics) Models Biological Prospective evaluation Animal science Pharmacokinetics Risk Factors Amphotericin B Amphotericin B Dose Neoplasms Drug Discovery Medicine Humans Urea Pharmacology (medical) Computer Simulation Dosing Child Pharmacology business.industry Body Weight Infant General Medicine gamma-Glutamyltransferase Drug Combinations Infectious Diseases Oncology Mycoses Anesthesia Child Preschool Creatinine Cyclosporine Kidney Diseases business Immunosuppressive Agents medicine.drug Deoxycholic Acid |
| Zdroj: | Chemotherapy. 53(2) |
| ISSN: | 1421-9794 |
| Popis: | In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (Css,trough) and plasma creatinine concentrations (Ccreat) were measured in 83 children (age: 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB Css,trough were identified by determining the probability of large (>24%, 75th percentile) increases in Ccreat after 6 days of AmB for a series of Css,trough ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76–1.05 mg/l Css,trough range provided the maximum concentrations that still had a low probability (p < 0.29) of adverse renal effects. 1 mg/kg/day AmB produces Css,trough within this range for children weighing 25–45 kg. Lighter children (10–25 kg) require higher AmB doses (1.25–1.5 mg/kg/day) to achieve target Css,trough, while heavier children (45–55 kg) require lower doses (0.75 mg/kg/day). These starting dose guidelines may require individualization and prospective evaluation. |
| Databáze: | OpenAIRE |
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