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Clinical Trial
Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.
- Emma J Love, Ludovic Pelligand, Polly M Taylor, Joanna C Murrell, and John W Sear.
- School of Veterinary Sciences, University of Bristol, Langford, UK.
- Vet Anaesth Analg. 2015 Jan 1; 42 (1): 17-29.
ObjectiveDescribe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects.Study DesignSingle phase non-blinded study.AnimalsSix dedicated research horses, aged 3-10 years and weighing 480-515 kg.MethodsThermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg(-1) buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg(-1) IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and 2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration-time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model.ResultsPlasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8-12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34-2.45 ng mL(-1) .Conclusions And Clinical RelevanceThe suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study.© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
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