Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

Vet Anaesth Analg. 2008 May;35(3):256-64. doi: 10.1111/j.1467-2995.2007.00379.x. Epub 2008 Feb 18.

Abstract

Objective: To assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs.

Study design: Randomized experimental trial.

Animals: Seven healthy male neutered Beagles aged 12.13 +/- 1.2 months and weighing 11.72 +/- 1.10 kg.

Methods: The study was a randomized Latin square block design. Dogs were randomly assigned to receive hydromorphone hydrochloride 0.1 mg kg(-1) or 0.5 mg kg(-1) IV (n = 4 dogs) or 0.1 mg kg(-1) (n = 6) or 0.5 mg kg(-1) (n = 5) SC on separate occasions with a minimum 14-day washout between experiments. Blood was sampled via a vascular access port at serial intervals after drug administration. Serum was analyzed by mass spectrometry. Pharmacokinetic parameters were determined with computer software.

Results: Serum concentrations of hydromorphone decreased quickly after both routes of administration of either dose. The serum half-life, clearance, and volume of distribution after IV hydromorphone at 0.1 mg kg(-1) were 0.57 hours (geometric mean), 106.28 mL minute(-1) kg(-1), and 5.35 L kg(-1), and at 0.5 mg kg(-1) were 1.00 hour, 60.30 mL minute(-1) kg(-1), and 5.23 L kg(-1), respectively. The serum half-life after SC hydromorphone at 0.1 mg kg(-1) and 0.5 mg kg(-1) was 0.66 hours and 1.11 hours, respectively.

Conclusions and clinical relevance: Hydromorphone has a short half-life, suggesting that frequent dosing intervals are needed. Based on pharmacokinetic parameters calculated in this study, 0.1 mg kg(-1) IV or SC q 2 hours or a constant rate infusion of hydromorphone at 0.03 mg kg(-1) hour(-1) are suggested for future studies to assess the analgesic effect of hydromorphone.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics*
  • Animals
  • Area Under Curve
  • Dogs
  • Half-Life
  • Hydromorphone / blood
  • Hydromorphone / pharmacokinetics*
  • Male

Substances

  • Analgesics, Opioid
  • Hydromorphone