Population pharmacokinetics of arbekacin in different infectious disease settings and evaluation of dosing regimens

Hagihara, Mao; Kato, Hideo; Hamada, Yukihiro; Hirai, Jun; Sakanashi, Daisuke; Suematsu, Hiroyuki; Nishiyama, Naoya; Koizumi, Yusuke; Yamagishi, Yuka; Matsuura, Keiichi

doi:10.1016/j.jiac.2016.03.008

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Hence, we could not assess the infection type as PK parameter covariates. We think, and as a previous study has revealed [ 27 ], the variety of infectious diseases is one of the influential factors in antimicrobial PK. However, this study was retrospective and small.…”

Section: Discussionmentioning

confidence: 81%

Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen

et al. 2017

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Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15–20 mg/kg). Hence, we evaluated the optimal initial dosing regimen of amikacin. Pharmacokinetic (PK) parameters were estimated using a population PK analysis. The pharmacodynamic (PD) target was a ratio of ≥8 between the concentration achieved 1 h after beginning the infusion (C peak) and the minimal inhibitory concentration (MIC) of the liable bacteria. Based on the population PK parameters, we simulated individual C peak for several dosing regimens by Monte Carlo method and analyzed the C peak/MIC ratio for MICs from 0.5 to 32 μg/mL. This study included 35 infected patients (25 males), with a median (range) age and body weight of 70 (15–95) years and 49.5 (32.5–78) kg, respectively. A two-compartment model was used, and total body clearance (CL) significantly correlated with creatinine clearance, and volume of distribution (V d) with body weight. Regarding the probability to achieve a C peak/MIC of ≥8, the 15 mg/kg regimen was sufficient to achieve the PK/PD target in ≥90% of patients for a MIC of 4 μg/mL or less. The cumulative fraction of response in Pseudomonas aeruginosa was that 76% of patients achieved a C peak/MIC of 8 with the amikacin dosage of 15 mg/kg/day. We suggest that the 15-mg/kg once-daily dosage of amikacin be recommended as the initial dosage. As its maintenance dosage, the 15 mg/kg/day amikacin dosage is needed for a MIC of ≤4 μg/mL, and amikacin monotherapy for a MIC of ≥8 μg/mL should be avoided.

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Section: Discussionmentioning

confidence: 81%

Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen

et al. 2017

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“…Three population pharmacokinetic models describing arbekacin disposition following i.v. administration have been developed (6)(7)(8). Similar to our model, as would be expected given the reported high (greater than 85% [9]) proportion of unchanged drug collected in urine, all three of these models describe a relationship between arbekacin clearance and CLcrn.…”

Section: Resultsmentioning

confidence: 83%

“…The analysis data sets described by Tanigawara et al and Hagihara et al, which contained data from both healthy volunteers and infected patients, allowed for pharmacokinetic differences between these two groups to be assessed. Tanigawara et al found that arbekacin volume of distribution was increased in infected patients relative to those of healthy volunteers, and Hagihara et al found that patients with sepsis had higher volumes of distribution than patients with pneumonia and other types of infections (7,8). The data set utilized for our covariate analysis only contained patients with infections; therefore, presence of infection could not be evaluated as a covariate.…”

Section: Resultsmentioning

confidence: 99%

Population Pharmacokinetic Analyses for Arbekacin after Administration of ME1100 Inhalation Solution

Lakota

Sato

Koresawa

et al. 2019

Antimicrob Agents Chemother

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ME1100, an inhalation solution of arbekacin, an aminoglycoside, is being developed for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia. The objective of these analyses was to develop a population pharmacokinetic model to describe the arbekacin concentration-time profile in plasma and epithelial lining fluid (ELF) following ME1100 administration. Data were obtained from a postmarketing study for an intravenous (i.v.) formulation of arbekacin, a phase 1 study of ME1100 in healthy volunteers, and a phase 1b study of ME1100 in mechanically ventilated subjects with bacterial pneumonia. Data from the postmarketing study were utilized to develop a population pharmacokinetic model following i.v. administration, and this model was subsequently utilized as the foundation for development of the model characterizing arbekacin disposition following inhalation of ME1100. The final model utilized two compartments for both plasma and ELF disposition, with movement of arbekacin between the ELF and plasma parameterized using linear first-order rate constants. A bioavailability term was included for the inhalational route of administration, which was estimated to be 19.5% for a typical subject. The model included normalized creatinine clearance (CLcrn) and weight as covariates on arbekacin clearance: CL ϭ (weight/52.2) 0.855 ·[(CLcrn-77)·0.0289 ϩ 2.32]. The model simultaneously described arbekacin concentrations following both i.v. and inhaled administration and provided acceptable fits to the plasma and ELF data (r 2 of 0.922 and 0.557 for observed versus fitted concentrations, respectively). The developed model will be useful for conducting future analyses to support ME1100 dose selection.

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Computational Approaches in Preclinical Studies on Drug Discovery and Development

Zhou

et al. 2020

Front. Chem.

210

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Because undesirable pharmacokinetics and toxicity are significant reasons for the failure of drug development in the costly late stage, it has been widely recognized that drug ADMET properties should be considered as early as possible to reduce failure rates in the clinical phase of drug discovery. Concurrently, drug recalls have become increasingly common in recent years, prompting pharmaceutical companies to increase attention toward the safety evaluation of preclinical drugs. In vitro and in vivo drug evaluation techniques are currently more mature in preclinical applications, but these technologies are costly. In recent years, with the rapid development of computer science, in silico technology has been widely used to evaluate the relevant properties of drugs in the preclinical stage and has produced many software programs and in silico models, further promoting the study of ADMET in vitro. In this review, we first introduce the two ADMET prediction categories (molecular modeling and data modeling). Then, we perform a systematic classification and description of the databases and software commonly used for ADMET prediction. We focus on some widely studied ADMT properties as well as PBPK simulation, and we list some applications that are related to the prediction categories and web tools. Finally, we discuss challenges and limitations in the preclinical area and propose some suggestions and prospects for the future.

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Population pharmacokinetics of arbekacin in different infectious disease settings and evaluation of dosing regimens

Cited by 3 publications

References 22 publications

Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen

Evaluation of Amikacin Pharmacokinetics and Pharmacodynamics for Optimal Initial Dosing Regimen

Population Pharmacokinetic Analyses for Arbekacin after Administration of ME1100 Inhalation Solution

Computational Approaches in Preclinical Studies on Drug Discovery and Development

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