Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses |
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| Institution: | 1. University of Georgia, College of Veterinary Medicine, Athens, GA, USA;2. K.L. Maddy Equine Analytical Chemistry Laboratory, University of California–Davis, School of Veterinary Medicine, Davis, CA, USA;1. Willows Veterinary Centre & Referral Service, Shirley, Solihull, UK;2. Department of Applied Physics/Electro-Optics, Jerusalem College of Technology, Yerushalayim, Israel;1. Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA;2. Department of Anesthesia, Montreal Children’s Hospital, McGill University, Montreal, QC, Canada;3. Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA;4. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA;5. Department of Anesthesiology and Pain Management, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina;1. Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA;2. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA;1. Anesthesiology and Pain Management, Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, 2015 SW 16th Av, P.O. Box 1000123, Gainesville, FL 32610-0123, USA;2. Department of Anesthesiology and Pain Management, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina |
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| Abstract: | ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg?1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg?1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (fR), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute?1 kg?1 and 1125 ± 309 mL kg?1. The t1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL?1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration. |
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| Keywords: | analgesia equine opioid pharmacodynamics pharmacokinetics pharmacology |
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