Comparison of microbiologie and high-performance liquid chromatography assays to determine plasma concentrations, pharmacokinetics, and bioavailability of erythromycin base in plasma of foals after intravenous or intragastric administration

Jeffrey Lakritz From the Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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 DVM, PhD
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W. David Wilson From the Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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 BVMS, MS
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Judith E. Mihalyi From the Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Abstract

Objective

To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A.

Animals

6 healthy foals that were 2 to 4 months old.

Procedure

Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method. Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared.

Results

Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and Ke1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals.

Conclusions and Clinical Relevance

The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates. (Am J Vet Res 1999;60:414-419)

Abstract

Objective

To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A.

Animals

6 healthy foals that were 2 to 4 months old.

Procedure

Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method. Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared.

Results

Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and Ke1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals.

Conclusions and Clinical Relevance

The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates. (Am J Vet Res 1999;60:414-419)

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