Abstract
The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine-3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine-6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady-state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min −1 kg −1 , respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.
| Original language | English (US) |
|---|---|
| Journal | Journal of Veterinary Pharmacology and Therapeutics |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- horse
- metabolism
- morphine
- pharmacodynamics
- pharmacokinetics
ASJC Scopus subject areas
- Pharmacology
- veterinary(all)
Cite this
Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses. / Hamamoto-Hardman, Briana D.; Steffey, Eugene; Weiner, Daniel; McKemie, Daniel S.; Kass, Philip H; Knych, Heather K.
In: Journal of Veterinary Pharmacology and Therapeutics, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses
AU - Hamamoto-Hardman, Briana D.
AU - Steffey, Eugene
AU - Weiner, Daniel
AU - McKemie, Daniel S.
AU - Kass, Philip H
AU - Knych, Heather K
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine-3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine-6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady-state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min −1 kg −1 , respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.
AB - The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine-3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine-6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady-state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min −1 kg −1 , respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.
KW - horse
KW - metabolism
KW - morphine
KW - pharmacodynamics
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85063596954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063596954&partnerID=8YFLogxK
U2 - 10.1111/jvp.12759
DO - 10.1111/jvp.12759
M3 - Article
C2 - 30919469
AN - SCOPUS:85063596954
JO - Journal of Veterinary Pharmacology and Therapeutics
JF - Journal of Veterinary Pharmacology and Therapeutics
SN - 0140-7783
ER -