Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs
IntroductionDosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet de...
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| Format: | Article |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2024.1362730/full |
| _version_ | 1797208829179461632 |
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| author | Candace Wimbish Alex M. Lynch Heather K. Knych Yu Ueda Kristen M. Messenger |
| author_facet | Candace Wimbish Alex M. Lynch Heather K. Knych Yu Ueda Kristen M. Messenger |
| author_sort | Candace Wimbish |
| collection | DOAJ |
| description | IntroductionDosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h.MethodsA prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software.ResultsA two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5–19.6) ng/mL. The median total body clearance was 30.4 (19.8–36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2–7.8) L/kg; and terminal elimination half-life was 11.2 (7.6–24.3) h.ConclusionHydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs. |
| first_indexed | 2024-04-24T09:45:01Z |
| format | Article |
| id | doaj.art-fd73c384309e4885893c8b9833811079 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-24T09:45:01Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-fd73c384309e4885893c8b98338110792024-04-15T04:23:34ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692024-04-011110.3389/fvets.2024.13627301362730Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogsCandace Wimbish0Alex M. Lynch1Heather K. Knych2Yu Ueda3Kristen M. Messenger4Department of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United StatesK.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United StatesIntroductionDosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h.MethodsA prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software.ResultsA two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5–19.6) ng/mL. The median total body clearance was 30.4 (19.8–36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2–7.8) L/kg; and terminal elimination half-life was 11.2 (7.6–24.3) h.ConclusionHydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.https://www.frontiersin.org/articles/10.3389/fvets.2024.1362730/fullconstant rate infusionhydromorphonedogpharmacokineticspainopioid |
| spellingShingle | Candace Wimbish Alex M. Lynch Heather K. Knych Yu Ueda Kristen M. Messenger Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs Frontiers in Veterinary Science constant rate infusion hydromorphone dog pharmacokinetics pain opioid |
| title | Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| title_full | Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| title_fullStr | Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| title_full_unstemmed | Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| title_short | Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| title_sort | pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs |
| topic | constant rate infusion hydromorphone dog pharmacokinetics pain opioid |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2024.1362730/full |
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