Pharmacokinetics of imipenem in dogs

Corrie W. Barker Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.

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Weijiang Zhang Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy.
Pesent address is TAP Pharmaceutical Products Inc, 675 N Field Dr, Lake Forest, IL 60045.

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Susan Sanchez Department of Medical Microbiology and Parasitology, College of Veterinary Medicine. Athens Diagnostic Laboratory, University of Georgia, Athens, GA, 30602.

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Steven C. Budsberg Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.

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F. Douglas Boudinot Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy.
Pesent address is the Department of Pharmaceutics, College of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298.

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M. A. McCrackin Stevenson Department of Small Animal Medicine and Surgery, College of Veterinary Medicine.
Department of Medical Microbiology and Parasitology, College of Veterinary Medicine.
Pesent address is Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, 903 S 4th St, Hamilton, MT 59840.

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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)

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