Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia.

Abstract

Doripenem is a parenteral carbapenem antibiotic with broad-spectrum antimicrobial activity. A pharmacokinetic (PK) analysis of a 1-h intravenous (i.v.) dose of 500 mg doripenem in ten clinically ill, elderly patients with nosocomial pneumonia (NP) was conducted. Concentrations of unchanged doripenem were measured in plasma using a validated liquid chromatography method coupled to a tandem mass spectrometry assay. Geometric means of maximum plasma concentration, area under the plasma concentration-time curve over the dosing interval at steady state, time to reach maximum plasma concentration, and terminal elimination half-life for 500 mg doripenem as a 1-h infusion were 22.40 μg/mL, 57.02 μgh/mL, 1.0h and 1.89h, respectively. In addition, a population PK analysis was performed to examine the influencing factors on the pharmacokinetics of doripenem and to estimate the time above minimum inhibitory concentration (T>MIC) by a post hoc Bayesian estimation. The effect of creatinine clearance was the most significant covariate on doripenem clearance. The estimated %T>MIC against a MIC of 2 μg/mL exceeded 40% in all patients. In the treatment of NP in elderly patients, a 1-h i.v. dose of 500 mg doripenem three times daily may provide a favourable antimicrobial effect against bacteria with MICs up to 2μg/mL and would therefore be a treatment option for NP.

• Authors: Masanori Harada, Naoki Inui, Takafumi Suda, Yutaro Nakamura, Toshihiro Wajima, Yumiko Matsuo, Kingo Chida
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 42 Issue 2 Pg. 149-54 (Aug 2013) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 23684002 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Carbapenems
• Doripenem

Topics

• Administration, Intravenous
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Carbapenems (administration & dosage, pharmacokinetics)
• Chromatography, Liquid
• Cross Infection (drug therapy)
• Doripenem
• Female
• Humans
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Models, Statistical
• Plasma (chemistry)
• Pneumonia, Bacterial (drug therapy)
• Tandem Mass Spectrometry
• Time Factors