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Pharmacokinetics of imipenem in dogs

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  • 1 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.
  • | 2 Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy.
  • | 3 Pesent address is TAP Pharmaceutical Products Inc, 675 N Field Dr, Lake Forest, IL 60045.
  • | 4 Department of Medical Microbiology and Parasitology, College of Veterinary Medicine. Athens Diagnostic Laboratory, University of Georgia, Athens, GA, 30602.
  • | 5 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.
  • | 6 Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy.
  • | 7 Pesent address is the Department of Pharmaceutics, College of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298.
  • | 8 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.
  • | 9 Department of Medical Microbiology and Parasitology, College of Veterinary Medicine.
  • | 10 Pesent address is Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, 903 S 4th St, Hamilton, MT 59840.

Abstract

Objective—To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro.

Animals—6 adult dogs.

Procedure—A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates.

Results—Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 µg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation halflife of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and 1.54 ± 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 ± 0.16 hours after IM and 0.83 ± 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes.

Conclusions and Clinical Relevance—Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli. (Am J Vet Res 2003;64:694–699)

Abstract

Objective—To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro.

Animals—6 adult dogs.

Procedure—A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates.

Results—Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 µg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation halflife of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and 1.54 ± 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 ± 0.16 hours after IM and 0.83 ± 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes.

Conclusions and Clinical Relevance—Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli. (Am J Vet Res 2003;64:694–699)