The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses

Rachel Reed, Michele Barletta, Krista Mitchell, Amanda Hanafi, Annie Bullington, Heather K Knych, Jane Quandt, Clare Ryan, Steeve Giguère

Research output: Contribution to journalArticle

Abstract

Objective: Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Study design: Masked, randomized, cross-over, Latin square design. Animals: A group of eight healthy adult horses Methods: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg –1 (LD), 0.04 mg kg –1 (MD), 0.08 mg kg –1 (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (f R ) and rectal temperature, and analyzed using mixed-effects linear models. Results: Mean (± standard deviation) hydromorphone terminal half-life (t 1/2 ), systemic clearance and apparent volume of distribution at steady state (Vd ss ) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg –1 minute –1 , and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg –1 for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment. Conclusions: Hydromorphone exhibited a short t 1/2 , rapid clearance and large Vd ss in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, f R and rectal temperature. Clinical relevance: Hydromorphone 0.04 mg kg –1 provided clinically relevant thermal antinociception with minimal adverse effects.

Original languageEnglish (US)
JournalVeterinary Anaesthesia and Analgesia
DOIs
StatePublished - Jan 1 2019

Fingerprint

Hydromorphone
pharmacology
pharmacokinetics
Horses
Pharmacokinetics
horses
heart rate
respiratory rate
heat
temperature
Hot Temperature
Therapeutics
half life
Heart Rate
experimental design
linear models
Respiratory Rate
adverse effects
heat treatment
Temperature

Keywords

  • analgesia
  • horses
  • hydromorphone
  • opioid
  • pharmacodynamics
  • pharmacokinetics

ASJC Scopus subject areas

  • veterinary(all)

Cite this

The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses. / Reed, Rachel; Barletta, Michele; Mitchell, Krista; Hanafi, Amanda; Bullington, Annie; Knych, Heather K; Quandt, Jane; Ryan, Clare; Giguère, Steeve.

In: Veterinary Anaesthesia and Analgesia, 01.01.2019.

Research output: Contribution to journalArticle

Reed, Rachel ; Barletta, Michele ; Mitchell, Krista ; Hanafi, Amanda ; Bullington, Annie ; Knych, Heather K ; Quandt, Jane ; Ryan, Clare ; Giguère, Steeve. / The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses. In: Veterinary Anaesthesia and Analgesia. 2019.
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abstract = "Objective: Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Study design: Masked, randomized, cross-over, Latin square design. Animals: A group of eight healthy adult horses Methods: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg –1 (LD), 0.04 mg kg –1 (MD), 0.08 mg kg –1 (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (f R ) and rectal temperature, and analyzed using mixed-effects linear models. Results: Mean (± standard deviation) hydromorphone terminal half-life (t 1/2 ), systemic clearance and apparent volume of distribution at steady state (Vd ss ) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg –1 minute –1 , and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg –1 for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment. Conclusions: Hydromorphone exhibited a short t 1/2 , rapid clearance and large Vd ss in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, f R and rectal temperature. Clinical relevance: Hydromorphone 0.04 mg kg –1 provided clinically relevant thermal antinociception with minimal adverse effects.",
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AU - Reed, Rachel

AU - Barletta, Michele

AU - Mitchell, Krista

AU - Hanafi, Amanda

AU - Bullington, Annie

AU - Knych, Heather K

AU - Quandt, Jane

AU - Ryan, Clare

AU - Giguère, Steeve

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Study design: Masked, randomized, cross-over, Latin square design. Animals: A group of eight healthy adult horses Methods: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg –1 (LD), 0.04 mg kg –1 (MD), 0.08 mg kg –1 (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (f R ) and rectal temperature, and analyzed using mixed-effects linear models. Results: Mean (± standard deviation) hydromorphone terminal half-life (t 1/2 ), systemic clearance and apparent volume of distribution at steady state (Vd ss ) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg –1 minute –1 , and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg –1 for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment. Conclusions: Hydromorphone exhibited a short t 1/2 , rapid clearance and large Vd ss in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, f R and rectal temperature. Clinical relevance: Hydromorphone 0.04 mg kg –1 provided clinically relevant thermal antinociception with minimal adverse effects.

AB - Objective: Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Study design: Masked, randomized, cross-over, Latin square design. Animals: A group of eight healthy adult horses Methods: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg –1 (LD), 0.04 mg kg –1 (MD), 0.08 mg kg –1 (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (f R ) and rectal temperature, and analyzed using mixed-effects linear models. Results: Mean (± standard deviation) hydromorphone terminal half-life (t 1/2 ), systemic clearance and apparent volume of distribution at steady state (Vd ss ) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg –1 minute –1 , and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg –1 for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment. Conclusions: Hydromorphone exhibited a short t 1/2 , rapid clearance and large Vd ss in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, f R and rectal temperature. Clinical relevance: Hydromorphone 0.04 mg kg –1 provided clinically relevant thermal antinociception with minimal adverse effects.

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KW - horses

KW - hydromorphone

KW - opioid

KW - pharmacodynamics

KW - pharmacokinetics

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