Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients
| Autor: | Paul Jarosinski, William W. Hope, Ihor Bekersky, Donald N. Buell, Nita L. Seibel, Thomas J. Walsh, Corina E. Gonzalez, Aziza T. Shad, Andreas H. Groll, Lauren V. Wood |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Antifungal Agents Neutropenia Dose Vomiting 030106 microbiology Population Pharmacology Gastroenterology Immunocompromised Host 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics Amphotericin B Internal medicine medicine Humans Pharmacology (medical) Child Infusions Intravenous education education.field_of_study Creatinine business.industry medicine.disease Treatment Outcome Infectious Diseases Tolerability chemistry Child Preschool Female Azotemia medicine.symptom business medicine.drug |
| Zdroj: | ANTIMICROBIAL AGENTS AND CHEMOTHERAPY |
| Popis: | The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population ( P = 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 μg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|