Pharmacokinetics Of Doripenem In Pediatric Patients With Cystic Fibrosis

Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbapenems (i.e., doripenem, imipenem-cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200-300 mg/kg/day divided every 6 hr, maximum 8-12 g/day. In vitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid development of resistance.

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“…The %T > MIC of 4 mg/L for P. aeruginosa was shown to be 63% of the dosing interval (Tables 1 and 4). 43, 44…”

Section: Introductionmentioning

confidence: 99%

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. aztreonam and carbapenems

Zobell

Young

Waters

et al. 2012

Pediatric Pulmonology

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“…13 No serious adverse effects were reported in this study. 13 The potential microbiological efficacy of doripenem in CF against P. aeruginosa and Burkholderia cepacia was reported in two studies showing the lowest MIC for 90% of isolates (MIC 90 ) values of tested antibiotics. 15,16 Based on this information, we chose to utilize intermittent extended infusion doripenem (90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day) in these three patients.…”

Section: Discussionmentioning

confidence: 56%

“…8,11 Intermittent extended infusion doripenem has been shown in two pharmacokinetic/pharmacodynamic studies involving CF patients, as well as described in the summary of product characteristics for doripenem to have the potential to be effective in the treatment of APEs secondary to pseudomonal isolates. [12][13][14] A small pharmacokinetic/ pharmacodynamic study utilizing intermittent extended infusion doripenem at 30 mg/kg/dose, (maximum 1,000 mg), infused over 4 hr, demonstrated that the percentage of time which doripenem serum concentrations remained above the MIC (% T > MIC) of P. aeruginosa of 4 mcg/ml was 67% of the dosing interval. 13 No serious adverse effects were reported in this study.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] A small pharmacokinetic/ pharmacodynamic study utilizing intermittent extended infusion doripenem at 30 mg/kg/dose, (maximum 1,000 mg), infused over 4 hr, demonstrated that the percentage of time which doripenem serum concentrations remained above the MIC (% T > MIC) of P. aeruginosa of 4 mcg/ml was 67% of the dosing interval. 13 No serious adverse effects were reported in this study. 13 The potential microbiological efficacy of doripenem in CF against P. aeruginosa and Burkholderia cepacia was reported in two studies showing the lowest MIC for 90% of isolates (MIC 90 ) values of tested antibiotics.…”

Section: Discussionmentioning

confidence: 99%

“…17 Finally, continuous infusion regimens require less handling than intermittent extended infusions, which may be advantageous for home intravenous treatments. 17 However, we decided to utilize intermittent extended infusion doripenem in the above patient cases due to the acute meropenem shortage because doripenem has very similar PK and anti-microbiological efficacy and activity as meropenem 4 ; dosing information has been published in the utilization of intermittent extended infusion doripenem in pediatric and adult CF patients 4,8,[12][13][14] ; no continuous infusion doripenem regimen in CF has been published to date 17 ; and no doripenem bioassay is available at our institution to allow optimization of doripenem C ss to maintain adequate T > MIC and C ss : MIC parameters (Zobell et al, in press).…”

Section: Discussionmentioning

confidence: 99%

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The Use of Doripenem in Pediatric Cystic Fibrosis Patients in Case of Meropenem Shortages

Zobell

Kemper

Young

2013

Pediatric Pulmonology

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Ceftazidime is the only anti-pseudomonal beta-lactam that has been reported to be administered by extended infusion in pediatric cystic fibrosis (CF) patients. A small pediatric pharmacokinetic/pharmacodynamic study has been published regarding the use of intermittent extended infusion doripenem in the treatment of an acute pulmonary exacerbation (APE) in pediatric CF patients; however, clinical use of intermittent extended infusion doripenem in pediatric CF patients has not been previously reported. We present three cases administering intermittent extended infusion doripenem in pediatric CF patients for the treatment of an APE in the case of replacing meropenem due to shortage. The delivery of beta-lactam antibiotics via intermittent extended infusion should be considered in order to optimize the pharmacodynamics of beta-lactams in the treatment of an APE.

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Pharmacokinetics Of Doripenem In Pediatric Patients With Cystic Fibrosis

Cited by 2 publications

References 0 publications

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. aztreonam and carbapenems

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. aztreonam and carbapenems

The Use of Doripenem in Pediatric Cystic Fibrosis Patients in Case of Meropenem Shortages

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