Comparison of microbiologic 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

J. Lakritz, William D Wilson, J. E. Mihalyi

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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 over-estimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e1)) 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.

Original languageEnglish (US)
Pages (from-to)414-419
Number of pages6
JournalAmerican Journal of Veterinary Research
Volume60
Issue number4
StatePublished - 1999

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intragastric administration
erythromycin
Erythromycin
intravenous injection
foals
Biological Availability
pharmacokinetics
bioavailability
Pharmacokinetics
high performance liquid chromatography
High Pressure Liquid Chromatography
assays
Biological Assay
bioassays
methodology
Rhodococcus equi
Microbial Sensitivity Tests
Cross-Over Studies
minimum inhibitory concentration
Area Under Curve

ASJC Scopus subject areas

  • veterinary(all)

Cite this

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title = "Comparison of microbiologic 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",
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 over-estimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e1)) 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.",
author = "J. Lakritz and Wilson, {William D} and Mihalyi, {J. E.}",
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T1 - Comparison of microbiologic 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

AU - Lakritz, J.

AU - Wilson, William D

AU - Mihalyi, J. E.

PY - 1999

Y1 - 1999

N2 - 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 over-estimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e1)) 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.

AB - 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 over-estimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and K(e1)) 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.

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