title: Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.
abstract: OBJECTIVE
  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 (r(2) =0.997) and urine (r(2) =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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Medicine, National University Hospital, Singapore.
authors.forename: Zuraidah
authors.initials: Z
authors.lastname: Sulaiman
authors.affiliation: Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Llorin
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kim-Hor
authors.initials: KH
authors.lastname: Hee
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Lawrence Soon-U
authors.initials: LS
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Department of Medicine, National University Hospital, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Dale A
authors.initials: DA
authors.lastname: Fisher
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX, USA vtam@uh.edu.
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Tam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D000077727:Ertapenem; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010045:Outpatients; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014552:Urinary Tract Infections / Q000188:drug therapy*; D014556:Urine / Q000737:chemistry; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem
keywords: Monte Carlo simulation; maximum likelihood expectation maximization; population modelling