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Differences in the Pharmacokinetics of Gentamicin between Oncology and Nononcology Pediatric Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Univ Queensland, Sch Pharm, Brisbane, Qld, Australia.
Univ Queensland, Sch Pharm, Brisbane, Qld, Australia.
Queensland Childrens Hosp, Brisbane, Qld, Australia.
Univ Queensland, Sch Pharm, Brisbane, Qld, Australia;Certara Strateg Consulting, Princeton, NJ USA.
2020 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 64, no 2, article id e01730-19Article in journal (Refereed) Published
Abstract [en]

Dosing gentamicin in pediatric patients can be difficult due to its narrow therapeutic index. A significantly higher percentage of fat mass has been observed in children receiving oncology treatment than in those who are not. Differences in the pharmacokinetics of gentamicin between oncology and nononcology pediatric patients and individual dosage requirements were evaluated in this study, using normal fat mass (NFM) as a body size descriptor. Data from 423 oncology and 115 nononcology patients were analyzed. Differences in drug disposition were observed between the oncology and nononcology patients, with oncology patients having a 15% lower central volume of distribution and 32% lower intercompartmental clearance. Simulations based on the population pharmacokinetic model demonstrated low exposure target attainment in all individuals at the current clinical recommended starting dose of 7.5 mg/kg of body weight once daily, with 57.4% of oncology and 35.7% of nononcology subjects achieving a peak concentration (C-max) of >= 25 mg/liter and 64.3% of oncology and 65.6% of nononcology subjects achieving an area under the concentration-time curve at 24 h postdose (AUC(24)) of mg.h/liter after the first dose. Based on simulations, the extent of the impact of differences in drug disposition between the two cohorts appeared to be dependent on the exposure target under examination. Greater differences in achieving a C-max target of >25 mg/liter than an AUC(24) target of >= 70 mg.h/liter between the cohorts was observed. Further investigation into whether differences in the pharmacokinetics of gentamicin between oncology and nononcology patients are a consequence of changes in body composition is required.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2020. Vol. 64, no 2, article id e01730-19
Keywords [en]
pediatrics, gentamicin, NONMEM, body composition, normal fat mass
National Category
Pediatrics Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-407142DOI: 10.1128/AAC.01730-19ISI: 000509748200025PubMedID: 31712209OAI: oai:DiVA.org:uu-407142DiVA, id: diva2:1415861
Available from: 2020-03-20 Created: 2020-03-20 Last updated: 2020-03-20Bibliographically approved

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