Pharmacokinetics of single-dose doripenem in adults with cystic fibrosis

J Clin Pharmacol. 2012 Nov;52(11):1645-53. doi: 10.1177/0091270011427564. Epub 2011 Dec 14.

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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Carbapenems / administration & dosage
  • Carbapenems / blood
  • Carbapenems / pharmacokinetics*
  • Cystic Fibrosis / metabolism*
  • Doripenem
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pseudomonas aeruginosa / drug effects
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Doripenem