Pharmacokinetics of Single-Dose Doripenem in Adults With Cystic Fibrosis.
ABSTRACT The pharmacokinetics of doripenem and doripenem-M-1 (inactive metabolite) were evaluated in an open-label, 2-period, single-sequence study in which single 1-g and 2-g doses of doripenem were administered intravenously over 4 hours to adult patients with cystic fibrosis (CF). The systemic exposure to doripenem and doripenem-M-1, as measured by observed apparent maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), increased approximately proportionally to the increase in dose. Other pharmacokinetic parameters of doripenem and doripenem-M-1, including clearance, volume of distribution, and elimination half-life, were similar for the 1-g and 2-g doses. The results from this study were also compared with those from a previous study in adult healthy volunteers (HVs) without CF, from a previously conducted pharmacokinetic study, who received single doses of 500 mg and 1 g doripenem administered over 4 hours. The pharmacokinetics of doripenem in adult patients with CF are similar to those from adult HVs, noting some differences in the disposition when comparing body mass index-adjusted pharmacokinetic parameters.
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ABSTRACT: Ceftazidime is the only anti-pseduomonal 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. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.Pediatric Pulmonology 05/2013; · 2.38 Impact Factor
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ABSTRACT: 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. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.Pediatric Pulmonology 08/2012; · 2.38 Impact Factor