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DOI: 10.48087/BJMS.2026.130408
Authors: Fatima Zohra BOUAOUA¹, Houari TOUMI², Karim BOULESBIAAT³,Habiba FETATI², Hocine GACEM³, Farida BOUCHNAK⁴, Abdelrahmane ABDAOUI², Zahia HAZMOUNE¹, Badis FOUGHALI¹, Soumia BOUDJEMAA³, Sabah BENBOUDIAF¹, Fatma Zohra BOUDIA², Rafika LAICHE³, Faiza BOUCHALA⁵, Kamel MANSOURI⁴
Affiliations: 1- Faculté de médecine, Université Constantine 3 – Salah Boubnider, Algérie. 2- Faculté de médecine, Université d’Oran 1 Ahmed Ben Bella, Algérie. 3- Faculté de médecine, Université de Batna 2 – Mostefa Ben Boulaïd, Algérie. 4- Faculté de médecine, Université d’Alger 1 Benyoucef Benkhedda, Algérie. 5- Faculté de médecine, Université Ferhat Abbas Sétif 1, Algérie.
Abstract
Introduction: Amikacin is a bactericidal aminoglycoside widely used in the treatment of severe infections caused by multidrug-resistant Gram-negative bacilli. Its clinical use is limited by significant interindividual pharmacokinetic variability and the risk of nephrotoxicity and ototoxicity. Its narrow therapeutic window complicates dose individualization, making it challenging to optimize efficacy while minimizing toxicity. The objective of this study was to develop an initial dose adjustment approach for amikacin based on a population pharmacokinetic (PKpop) model integrated with therapeutic drug monitoring (TDM), in order to propose optimized dosing regimens. Materials and Methods: A retrospective and prospective study was conducted in hospitalized patients receiving amikacin. Plasma concentrations were measured using an immunoenzymatic method and modeled using a nonlinear mixed-effects approach. Covariates assessed included body weight and creatinine clearance. Monte Carlo simulations were performed on 1,000 virtual patients to evaluate the probability of target attainment for minimum (Cmin) and maximum (Cmax) plasma concentrations. Results: Among the 50 patients with normal renal function included (MDRD: 115.8 ± 13 mL/min), a one-compartment model was selected, estimating a population volume of distribution (Vpop) of 23.3 L, 70.8 L, and 21.5 L, and a population clearance (Clpop) of 2.4 L/h, 6.5 L/h, and 2.7 L/h for children, adults, and elderly patients, respectively. Relative standard errors were low, indicating good model precision and stability. Simulations demonstrated that optimal doses to achieve target concentrations varied by age group: 50 mg/kg every 24 hours for adults, and 20 mg/kg every 36–48 hours for children and elderly patients. Discussion: These findings suggest that standard dosing regimens are often insufficient to meet efficacy and safety targets. Integrating population pharmacokinetics with therapeutic drug monitoring enables dose individualization, improves treatment efficacy, and reduces the risk of toxicity.
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Keywords: Amikacin, population pharmacokinetics, therapeutic drug monitoring, simulation.