Pharmacokinetics of hydromorphone hydrochloride in healthy dogs

Abstract

ObjectiveTo assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. Study designRandomized experimental trial. AnimalsSeven healthy male neutered Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg. MethodsThe 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. ResultsSerum 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 relevanceHydromorphone 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.