Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

S. Y. Byun, J. W. Jeong, J. H. Choi, K. P. Lee, H. Y. Youn, H. J. Maeng, K. H. Song, T. S. Koo, Kyoung Won Seo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 μg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.

Original languageEnglish (US)
Pages (from-to)560-565
Number of pages6
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume39
Issue number6
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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meropenem
hemodialysis
Beagle
pharmacokinetics
Renal Dialysis
Pharmacokinetics
Dogs
dogs
Dialysis Solutions
renal failure
dialysis
Renal Insufficiency
Dialysis
urine
carbapenems
Urine
Vascular Access Devices
sepsis (infection)
Carbapenems
Veterinary Medicine

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis. / Byun, S. Y.; Jeong, J. W.; Choi, J. H.; Lee, K. P.; Youn, H. Y.; Maeng, H. J.; Song, K. H.; Koo, T. S.; Seo, Kyoung Won.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 39, No. 6, 01.12.2016, p. 560-565.

Research output: Contribution to journalArticle

Byun, S. Y. ; Jeong, J. W. ; Choi, J. H. ; Lee, K. P. ; Youn, H. Y. ; Maeng, H. J. ; Song, K. H. ; Koo, T. S. ; Seo, Kyoung Won. / Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis. In: Journal of Veterinary Pharmacology and Therapeutics. 2016 ; Vol. 39, No. 6. pp. 560-565.
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abstract = "Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 μg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21{\%} of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.",
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