Pharmacokinetics of cefepime and comparison with those of ceftiofur in horses

Mary Ann Guglick From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Charles G. MacAllister From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Cyril R. Clarke From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Robert Pollet From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Christinia Hague From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Jean Μ. Clarke From the Departments of Medicine and Surgery (Guglick, MacAllister), Anatomy, Pathology, and Pharmacology (Clarke CR, Hague), and Infectious Diseases and Physiology (Clarke JM), College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078; and Fort Dodge Laboratories, Fort Dodge, IA 50501 (Pollet).

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Abstract

Objective

To determine pharmacokinetics of IV, IM, and oral administration of cefepime in horses and to compare pharmacokinetics of IM administration of cefepime with those of ceftiofur sodium.

Animals

6 clinically normal adult horses.

Procedure

Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, IV; and 2.2 mg/kg, IM) and 1 dose of ceftiofur (2.2 mg/kg, IM). Two horses also received l-arginine, PO and IV, at doses identical to those contained in the cefepime dihydrochloride-l-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentrations.

Results

Pharmacokinetic analysis of disposition data indicated that IV administration data were best described by a 2-compartment open model, whereas IM administration data were best described by a 1-compartment absorption model. Median elimination half-life and volume of distribution after IV administration of cefepime were 125.7 minutes and 225 ml/kg, respectively. After IM administration of cefepime, mean maximal plasma concentration of (8.13 μg/ml) was reached at a mean time of 80 minutes. Absorption of cefepime after IM administration was complete, with a median bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in similar mean maximal plasma concentration (7.98 μg/ml) and mean time to this concentration (82 minutes). Cefepime was not detected in samples collected after oral administration. Adverse effects consisting principally of gastrointestinal disturbances were observed after oral and IM administration of cefepime and after 1 IM administration of ceftiofur.

Conclusions and Clinical Relevance

Cefepime, administered IV or IM at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sensitive organisms in horses. Further studies are needed to evaluate adverse effects on the gastrointestinal tract. (Am J Vet Res 1998;59:458–463)

Abstract

Objective

To determine pharmacokinetics of IV, IM, and oral administration of cefepime in horses and to compare pharmacokinetics of IM administration of cefepime with those of ceftiofur sodium.

Animals

6 clinically normal adult horses.

Procedure

Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, IV; and 2.2 mg/kg, IM) and 1 dose of ceftiofur (2.2 mg/kg, IM). Two horses also received l-arginine, PO and IV, at doses identical to those contained in the cefepime dihydrochloride-l-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentrations.

Results

Pharmacokinetic analysis of disposition data indicated that IV administration data were best described by a 2-compartment open model, whereas IM administration data were best described by a 1-compartment absorption model. Median elimination half-life and volume of distribution after IV administration of cefepime were 125.7 minutes and 225 ml/kg, respectively. After IM administration of cefepime, mean maximal plasma concentration of (8.13 μg/ml) was reached at a mean time of 80 minutes. Absorption of cefepime after IM administration was complete, with a median bioavailability of 1.11. Intramuscular administration of ceftiofur resulted in similar mean maximal plasma concentration (7.98 μg/ml) and mean time to this concentration (82 minutes). Cefepime was not detected in samples collected after oral administration. Adverse effects consisting principally of gastrointestinal disturbances were observed after oral and IM administration of cefepime and after 1 IM administration of ceftiofur.

Conclusions and Clinical Relevance

Cefepime, administered IV or IM at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sensitive organisms in horses. Further studies are needed to evaluate adverse effects on the gastrointestinal tract. (Am J Vet Res 1998;59:458–463)

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