Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation

Ghoneim, Ragia H.; Thabit, Abrar K.; Lashkar, Manar O.; Ali, Ahmed

doi:10.1186/s13052-021-01114-4

Cited by 10 publications

(14 citation statements)

References 14 publications

(20 reference statements)

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“…Population pharmacokinetic (PPK), combined with a Monte Carlo simulation, provide feasible technical support for solving initial dosage recommendations in clinical practice. In recent years, more and more related research has been reported, which further verifies the reliability and practicability of this method (Jaruratanasirikul et al, 2019;Ren et al, 2019;Ghoneim et al, 2021;Rinaldi et al, 2021;Tang Girdwood et al, 2022). Hence, the present study recommends initial dosages of sirolimus in pediatric patients with PIK3CD mutationrelated immunodeficiency disease based on PPK and a Monte Carlo simulation.…”

Section: Introductionsupporting

confidence: 68%

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

Chen

Wang²,

Lan³

et al. 2022

Front. Pharmacol.

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Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0.238 between children without and children with posaconazole. Without posaconazole, the initial dosages of sirolimus were 0.07, 0.06, 0.05, and 0.04 mg/kg/day for body weights of 10–14, 14–25, 25–50, and 50–60 kg, respectively. With posaconazole, the initial dosages of sirolimus were 0.02 mg/kg/day for body weights of 10–60 kg. This is the first attempt to build a sirolimus PPK model for recommending initial dosages in children with PIK3CD mutation-related immunodeficiency disease, thereby providing a reference for individualized clinical drug administration.

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Section: Introductionsupporting

confidence: 68%

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

Chen

Wang²,

Lan³

et al. 2022

Front. Pharmacol.

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“…Li et al reported population pharmacokinetics of polymyxin B and dosage optimization in renal transplant patients (Li et al, 2021). Ghoneim et al (2021) reported optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation. Wang et al (2021) reported population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and a model-informed dosing strategy.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation

et al. 2022

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The present study aimed to explore the population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency (SCID) undergoing hematopoietic stem cell transplantation (HSCT). Children with SCID undergoing HSCT treated with tacrolimus were enrolled for analysis. Population pharmacokinetics of tacrolimus was built up by a nonlinear mixed-effects model (NONMEM), and initial dose optimization of tacrolimus was simulated with the Monte Carlo method in children weighing <20 kg at different doses. A total of 18 children with SCID undergoing HSCT were included for analysis, with 130 tacrolimus concentrations. Body weight was included as a covariable in the final model. Tacrolimus CL/F was 0.36–0.26 L/h/kg from body weights of 5–20 kg. Meanwhile, we simulated the tacrolimus concentrations using different body weights (5–20 kg) and different dose regimens (0.1–0.8 mg/kg/day). Finally, the initial dose regimen of 0.6 mg/kg/day tacrolimus was recommended for children with SCID undergoing HSCT whose body weights were 5–20 kg. It was the first time to establish tacrolimus population pharmacokinetics in children with SCID undergoing HSCT; in addition, the initial dose optimization of tacrolimus was recommended.

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“…The results demonstrated that a Cmin of less than 2 mg/L decreased the risk of toxicity caused by gentamicin; thus, a gentamicin dose of 7.0 mg/kg once daily can be used to achieve a Cmin of less than 2 mg/L in the pediatric population [ 19 ]. Recently, the optimal gentamicin dosage in different pediatric age groups was investigated using population PK and Monte Carlo simulations [ 20 ]. Infants require daily doses of at least 4.0–8.0 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Gentamicin Pharmacokinetics and Optimal Dosage in Infant Patients: A Case Report and Literature Review

Kato

Hagihara

Matsuda

et al. 2022

IJERPH

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Gentamicin is an aminoglycoside antibiotic that is mostly used for the pediatric population. While the pediatric population is classified into neonates, infants, children, and adolescents based on developmental or maturational changes, infants are often overlooked in research. Three infant cases receiving gentamicin are presented to illustrate the pharmacokinetics and optimum dosage of gentamicin. Three infant patients received gentamicin (5.6–7.5 mg/kg/day) for urinary tract infections (UTIs) or bacteremia caused by Enterobacter aerogenes. The trough (Cmin) and peak (Cpeak) concentrations of gentamicin were 0.2–1.8 and 8.9 mg/L, respectively. The Cmin of a patient receiving gentamicin at 9.0 mg/kg/day was 3.3 mg/L, and the patient showed a decrease in urinary volume. The other two patients fully recovered from the infection and did not experience any adverse events. Additionally, we reviewed three studies regarding infant patients receiving gentamicin. The studies used gentamicin therapy for Gram-negative pathogen infections and UTIs caused by Escherichia coli and Enterococcus faecalis. The Cmin and Cpeak of patients receiving gentamicin at 2.2–7.5 mg/kg/day were 0.58–2.15 mg/kg and 4.67–8.88 mg/L, respectively. All patients were cured without any adverse events. Gentamicin dosages below 7.5 mg/kg/day may be effective and safe for use in infant patients. However, the optimal dosing regimen of gentamicin in infant patients is controversial, and limited data are available.

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Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation

Cited by 10 publications

References 14 publications

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease

Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation

Gentamicin Pharmacokinetics and Optimal Dosage in Infant Patients: A Case Report and Literature Review

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