Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses |
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| Institution: | 1. Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL, USA;2. Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA;3. Department of Molecular Biosciences, University of California Davis School of Veterinary Medicine, Davis, CA, USA;1. Veterinary Sciences Graduate Program, Department of Veterinary Medicine, Federal University of Paraná, Curitiba, PR, Brazil;2. Anatomy Department, Biological Science Sector, Federal University of Paraná, Curitiba, PR, Brazil;1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, USA;2. Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, USA |
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| Abstract: | ObjectivesTo determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses.Study designProspective, randomized, crossover study.AnimalsA group of six adult healthy horses weighing 585.2 ± 58.7 kg.MethodsEach 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.ResultsHydromorphone 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 relevanceHydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output. |
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| Keywords: | behavior cardiovascular horse hydromorphone pharmacodynamics pharmacokinetics |
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