Abstract
Amikacin is used as a therapy for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) who are resistant to macrolide antibiotics or have severe symptoms. This study aimed to characterize the pharmacokinetic properties of amikacin in patients with NTM-PD by developing a population pharmacokinetic model and to explore the optimal pharmacotherapy in patients with NTM-PD. For this study, all data were retrospectively collected. The amikacin pharmacokinetic properties were best described by a two-compartment model with first-order elimination. The estimated glomerular filtration rate and body weight were identified as significant covariates for clearance and the volume of distribution, respectively. A model-based simulation was conducted to explore the probability of reaching the target therapeutic range when various dose regimens were administered according to the body weight and renal function. The simulation results indicated that the amikacin dosage should be determined based on the body weight, and for patients who weigh over 70 kg, it is necessary to adjust the dose according to renal function. In conclusion, the optimal pharmacotherapy of amikacin for patients with NTM-PD was recommended based on the population pharmacokinetic model, which is expected to enable the personalization of drug therapy and improve the clinical outcomes of amikacin therapy.
Highlights
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic pulmonary disease caused by infection with nontuberculous mycobacteria (NTM) [1]
Macrolide antibiotics form the basis of therapy for NTM-PD, and patients with macrolide resistance or severe NTM-PD are treated with amikacin [4]
848 serum amikacin concentration-time data points were collected from 70 adult patients who received amikacin for the treatment of NTM-PD
Summary
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic pulmonary disease caused by infection with nontuberculous mycobacteria (NTM) [1]. Macrolide antibiotics form the basis of therapy for NTM-PD, and patients with macrolide resistance or severe NTM-PD are treated with amikacin [4]. Amikacin is an aminoglycoside antibiotic that is used for the treatment of severe infections caused by multidrug-resistant, aerobic Gram-negative bacteria that bind to bacterial 30S ribosomal subunits and leads to the disruption of normal protein synthesis and the production of nonfunctional or toxic peptides [5]. According to the mechanism of action, amikacin is used for the treatment of NTM-PD, and the recommended dose is 10–15 mg/kg once daily for patients with NTM infection [4]
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