Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses

Heather K Knych, Rick Arthur, Dan S. McKemie, Kelsey Seminoff, Briana Hamamoto-Hardman, Philip H Kass

Research output: Contribution to journalArticle

Abstract

Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and non-compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half-life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half-life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, LTB4 and 15-HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti-inflammatory following IV or oral administration of 2 g to horses.

Original languageEnglish (US)
JournalDrug Testing and Analysis
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Phenylbutazone
Pharmacokinetics
Biomarkers
horse
Intravenous Administration
urine
Horses
Oral Administration
biomarker
Blood
blood
Urine
Inflammation
Eicosanoids
Calcium Ionophores
drug
Half-Life
Lipopolysaccharides
Metabolites
Anti-Inflammatory Agents

Keywords

  • eicosanoids
  • horse
  • inflammation
  • pharmacokinetics
  • phenylbutazone

ASJC Scopus subject areas

  • Analytical Chemistry
  • Environmental Chemistry
  • Pharmaceutical Science
  • Spectroscopy

Cite this

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title = "Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses",
abstract = "Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and non-compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half-life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half-life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, LTB4 and 15-HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti-inflammatory following IV or oral administration of 2 g to horses.",
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T1 - Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses

AU - Knych, Heather K

AU - Arthur, Rick

AU - McKemie, Dan S.

AU - Seminoff, Kelsey

AU - Hamamoto-Hardman, Briana

AU - Kass, Philip H

PY - 2018/1/1

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N2 - Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and non-compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half-life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half-life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, LTB4 and 15-HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti-inflammatory following IV or oral administration of 2 g to horses.

AB - Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and non-compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half-life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half-life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, LTB4 and 15-HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti-inflammatory following IV or oral administration of 2 g to horses.

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