Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients.

Autor:	Hsaiky LM; Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA., Salinitri FD; Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA.; Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA., Wong J; Inpatient Pharmacy, Beaumont Hospital - Dearborn, Dearborn, MI, USA., Jennings ST; Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA., Desai NH; Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA., Lobkovich AM; Inpatient Pharmacy, Beaumont Hospital - Dearborn, Dearborn, MI, USA., Cha R; Pharmacy Professional Services, Beaumont Hospital - Dearborn, Dearborn, MI, USA.; Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Jazyk:	angličtina
Zdroj:	Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2019 Oct 01; Vol. 34 (10), pp. 1766-1772.
DOI:	10.1093/ndt/gfy166
Abstrakt:	Background: Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. Methods: This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. Results: Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h-∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. Conclusions: Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy. (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
Databáze:	MEDLINE
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