Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses

Objectives: To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Study design: Prospective, randomized, crossover study. Animals: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg^–1; treatment H0.025), hydromorphone (0.05 mg kg^–1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures ANOVA with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation. Results: Hydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute^–1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg^–1, 106 ± 21 mL minute^–1 kg^–1 and 8.0 ± 1.5 ng hour mL^–1, respectively. Conclusions and clinical relevance: Hydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.