Pharmacokinetics of pergolide after intravenous administration to horses

David I. Rendle School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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 BVSC, MVM
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Kris J. Hughes School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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 BVSc
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Gregory S. Doran Graham Centre for Agricultural Innovation, School of Agricultural and Wine Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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 PhD
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Scott H. Edwards School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.

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 BVMS, PhD

Abstract

OBJECTIVE To determine the pharmacokinetics of pergolide after IV administration to horses.

ANIMALS 8 healthy adult horses.

PROCEDURES Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods.

RESULTS After IV administration of pergolide, mean ± SD clearance, elimination half-life, and initial volume of distribution were 959 ± 492 mL/h/kg, 5.64 ± 2.36 hours, and 0.79 ± 0.32 L/kg, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE With an elimination half-life of approximately 6 hours, twice-daily dosing may be more appropriate than once-daily dosing to reduce peak-trough fluctuation in pergolide concentrations. Further pharmacodynamic and pharmacokinetic studies of pergolide and its metabolites will be necessary to determine plasma concentrations that correlate with clinical effectiveness to determine the therapeutic range for the treatment of pituitary pars intermedia dysfunction.

Abstract

OBJECTIVE To determine the pharmacokinetics of pergolide after IV administration to horses.

ANIMALS 8 healthy adult horses.

PROCEDURES Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods.

RESULTS After IV administration of pergolide, mean ± SD clearance, elimination half-life, and initial volume of distribution were 959 ± 492 mL/h/kg, 5.64 ± 2.36 hours, and 0.79 ± 0.32 L/kg, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE With an elimination half-life of approximately 6 hours, twice-daily dosing may be more appropriate than once-daily dosing to reduce peak-trough fluctuation in pergolide concentrations. Further pharmacodynamic and pharmacokinetic studies of pergolide and its metabolites will be necessary to determine plasma concentrations that correlate with clinical effectiveness to determine the therapeutic range for the treatment of pituitary pars intermedia dysfunction.

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