Jian Zhou, Z. Sulaiman, R. Llorin
Sep 1, 2014
Citations
2
Influential Citations
19
Citations
Quality indicators
Journal
The Journal of antimicrobial chemotherapy
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 (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.