Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis.
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 T1/2was 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.
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
S Y
SY
Byun
Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea.
J W
JW
Jeong
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
J H
JH
Choi
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
K P
KP
Lee
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
H Y
HY
Youn
College of Pharmacy, Gachon University, Incheon, Korea.
H J
HJ
Maeng
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea.
K H
KH
Song
Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Korea. kootae@cnu.ac.kr.
T S
TS
Koo
College of Veterinary Medicine, Chungnam National University, Daejeon, Korea. kwseo@cnu.ac.kr.
K W
KW
Seo
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004285:Dogs / Q000097:blood*; D006207:Half-Life; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D000077731:Meropenem; D006435:Renal Dialysis / Q000662:veterinary*; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem