Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections - Abstract

OBJECTIVES: Ertapenem is a broad-spectrum carbapenem antibiotic used to treat severe bacterial infections.

In view of its dosing convenience, it is increasingly used as outpatient therapy. The objective of this study was to determine the pharmacokinetics and renal disposition of ertapenem in outpatients with complicated urinary tract infections.

METHODS: Ertapenem was administered as a daily intravenous infusion of 1 g over 30 min. At steady-state, blood and urine samples were collected over one dosing interval. Drug concentrations in serum and urine were determined using a validated liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was used to characterize ertapenem serum and urine profiles. The likelihood of the standard dosing achieving a favourable pharmacokinetic-pharmacodynamic exposure was evaluated using Monte Carlo simulations.

RESULTS: Ten adult male patients were studied. Concentration-time profiles of ertapenem in both serum (r2 =0.997) and urine (r2 =0.982) were captured satisfactorily. Mean values for volume of distribution, clearance and elimination t½ were 4.8 L, 0.7 L/h and 6.1 h, respectively. A high ertapenem concentration (>128 mg/L) could be attained in the urine at 40% of the dosing interval.

CONCLUSIONS: The pharmacokinetics of ertapenem in serum and urine were characterized. Our simulations suggested that a sufficiently high ertapenem concentration could be achieved in urine to overcome low to intermediate resistance. Clinical investigations to validate our findings are warranted.

Written by:
Zhou J, Sulaiman Z, Llorin RM, Hee KH, Lee LS, Lye DC, Fisher DA, Tam VH.   Are you the author?
Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA; Department of Medicine, National University Hospital, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX, USA.  

Reference: J Antimicrob Chemother. 2014 Sep;69(9):2517-21.
doi: 10.1093/jac/dku143

PubMed Abstract
PMID: 24797063 Infections Section