title: 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.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Harada
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Wajima
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003428:Cross Infection / Q000188:drug therapy*; D000077726:Doripenem; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015233:Models, Statistical; D010949:Plasma / Q000737:chemistry; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem
keywords: Creatinine clearance; Doripenem; Nosocomial pneumonia; Pharmacokinetics; Population pharmacokinetic analysis