Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia

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 μg h/mL, 1.0 h and 1.89 h, 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 2 μg/mL and would therefore be a treatment option for NP.