Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers

Funatsu, Yohei; Hasegawa, Naoki; Fujiwara, Hiroshi; Namkoong, Ho; Asami, Takahiro; Tasaka, Sadatomo; Kimizuka, Yoshifumi; Kamata, Hirofumi; Ishii, Makoto; Iketani, Osamu; Ogata, Haruhiko; Iwata, Satoshi; Betsuyaku, Tomoko

doi:10.1016/j.jiac.2014.05.007

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…rifapentine (30) rifampicin (55) pyrazinamide (40) isoniazid (80) ethionamide (40) gsk1322322 (17) linezolid (67) zanamivir (36) telithromycin (115) solithromycin (30) s−013420 (28) roxithromycin (15) erythromycin (12) dirithromycin (25) clarithromycin (133) cethromycin (60) azythromycin (144) tigecycline (30) vancomycin (24) telavancin (20) teicoplanin (13) trovafloxacin (27) temafloxacin (32) sparfloxacin (57) rufloxacin (32) pefloxacin (10) opc−17116 (24) moxifloxacin (34) lomefloxacin (52) levofloxacin (237) gatifloxacin (15) garenoxacin (24) clinafloxacin (15) ciprofloxacin (81) iclaprim (24) cefuroxime axetil (26) ceftobiprole (24) ceftibuten (13) ceftazidime (15) cefpodoxime proxetil (12) cefpirome (8) cefepime (20) cefditoren (24) cefdinir (16) meropenem (78) ertapenem (30) biapenem (12) tazobactam (10) clavulanic acid (15) piperacillin (10) amoxycillin (15) voricona...…”

Section: Model Developmentmentioning

confidence: 99%

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

et al. 2015

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Purpose Obtaining pharmacologically relevant exposure levels of antibiotics in the epithelial lining fluid (ELF) is of critical importance to ensure optimal treatment of lung infections. Our objectives were to develop a model for the prediction of the ELF-plasma concentration ratio (EPR) of antibiotics based on their chemical structure descriptors (CSDs). Methods EPR data was obtained by aggregating ELF and plasma concentrations from historical clinical studies investigating antibiotics and associated agents. An elastic net regularized regression model was used to predict EPRs based on a large number of CSDs. The model was tuned using leave-one-drug-out cross validation, and the predictions were further evaluated using a test dataset. Results EPR data of 56 unique compounds was included. A high degree of variability in EPRs both between-and within drugs was apparent. No trends related to study design or pharmacokinetic factors could be identified. The model predicted 80% of the within-drug variability (R 2 WDV ) and 78.6% of drugs were within 3-fold difference from the observations. Key CSDs were related to molecular size and lipophilicity. When predicting EPRs for a test dataset the R 2 WDV was 75%. Conclusions This model is of relevance to inform dose selection and optimization during antibiotic drug development of agents targeting lung infections.

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Section: Model Developmentmentioning

confidence: 99%

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

et al. 2015

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“…Sampling was made with Bronchoalveolar Lavage in ALL Studies Except the Study of Arbekacin and Peramivir for Which Bronchoscopic Microsampling was Utilized Drug name Nr of subjects Nr of time points Time of last ELF sample (hours) Study conducted at steady state? Protein binding (%) EPR (log EPR) Reference Arbekacin 6 8 6 - 6 0.72 (-0.33) ( 6 ) Avibactam 42 4 8 + 8 0.35 (-1.05) ( 7 ) Ceftaroline 53 5 12 + 20 0.23 (-1.47) ( 8 ) Ceftolozane 25 5 8 + 20 0.59 (-0.53) ( 9 ) Eravacycline 20 4 12 + 83 6.44 (1.86) ( 10 ) GSK22510052 15 3 12 + 10 0.597 (-0.55) ( 11 ) Imipenem 16 4 3 + 20 0.53 (-0.63) ( 12 ) Lefamulin 12 4 8 - 87 5.7 (1.74) ( 13 ) Omadacycline 42 7 24 + 20 1.84 (0.61) ( 14 ) …”

Section: Resultsmentioning

confidence: 99%

Validation of a Model Predicting Anti-infective Lung Penetration in the Epithelial Lining Fluid of Humans

et al. 2018

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“… 93 , 96 In vitro analysis suggests that arbekacin in combination with aztreonam is an effective regimen against MDR P. aeruginosa , including metallo-β-lactamase-producing strains; 93 however, further studies are needed to show its applicability and safety in clinical practice. In PK studies, arbekacin has shown acceptable pulmonary tissue distribution and an adequate safety profile; 97 however, therapeutic plasma level monitoring is recommended to optimize its efficacy and minimize adverse effects, mainly nephrotoxicity. 93 …”

Section: Arbekacinmentioning

confidence: 99%

Pseudomonas aeruginosa ventilator-associated pneumonia management

Ramirez-Estrada¹,

Borgatta²,

Rello³

2016

IDR

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Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising.

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Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers

Cited by 11 publications

References 26 publications

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

Validation of a Model Predicting Anti-infective Lung Penetration in the Epithelial Lining Fluid of Humans

Pseudomonas aeruginosa ventilator-associated pneumonia management

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