Rachael L Hoh, Khursheed R Mama, Camilo J Morales, Daniel S McKemie, Philip H Kass, H K Knych
{"title":"丁丙诺啡经皮给药部位对马体内药代动力学及选择性药效学的影响。","authors":"Rachael L Hoh, Khursheed R Mama, Camilo J Morales, Daniel S McKemie, Philip H Kass, H K Knych","doi":"10.1016/j.vaa.2025.08.035","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses.</p><p><strong>Study design: </strong>Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study.</p><p><strong>Animals: </strong>Six (study 1) and eight (study 2) horses, aged 3-14 years.</p><p><strong>Methods: </strong>In study 1, horses were administered a single dose of buprenorphine (45 μg kg<sup>-1</sup>), applied to the neck, croup and stifle. Blood samples were collected at fixed time points and a skin biopsy taken at the final time point for buprenorphine concentration analysis. In study 2, horses were administered a single transdermal dose of buprenorphine (90 μg kg<sup>-1</sup>) applied to the neck (determined in study 1). Blood samples were collected and buprenorphine concentrations determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis performed. Pre- and post-drug-related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Mixed effects analysis of variance comparisons were performed to assess differences in pharmacodynamic parameters between baseline and each time point.</p><p><strong>Results: </strong>Plasma buprenorphine concentrations were highest after application to the neck and stifle. Transdermal application of 90 μg kg<sup>-1</sup> to the neck significantly (p < 0.05) increased thermal nociceptive thresholds from 3 hours and up to 36 hours after application. This corresponded with plasma buprenorphine concentrations ≥ 0.1 ng mL<sup>-1</sup>. Changes in locomotor activity, heart rate and borborygmi were minimal.</p><p><strong>Conclusions and clinical relevance: </strong>A thermal antinociceptive effect was observed after the transdermal delivery of 90 μg kg<sup>-1</sup> of buprenorphine, applied to the neck.</p>","PeriodicalId":23626,"journal":{"name":"Veterinary anaesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The impact of transdermal application site on pharmacokinetics and selected pharmacodynamics of buprenorphine in horses.\",\"authors\":\"Rachael L Hoh, Khursheed R Mama, Camilo J Morales, Daniel S McKemie, Philip H Kass, H K Knych\",\"doi\":\"10.1016/j.vaa.2025.08.035\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses.</p><p><strong>Study design: </strong>Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study.</p><p><strong>Animals: </strong>Six (study 1) and eight (study 2) horses, aged 3-14 years.</p><p><strong>Methods: </strong>In study 1, horses were administered a single dose of buprenorphine (45 μg kg<sup>-1</sup>), applied to the neck, croup and stifle. Blood samples were collected at fixed time points and a skin biopsy taken at the final time point for buprenorphine concentration analysis. In study 2, horses were administered a single transdermal dose of buprenorphine (90 μg kg<sup>-1</sup>) applied to the neck (determined in study 1). Blood samples were collected and buprenorphine concentrations determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis performed. Pre- and post-drug-related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Mixed effects analysis of variance comparisons were performed to assess differences in pharmacodynamic parameters between baseline and each time point.</p><p><strong>Results: </strong>Plasma buprenorphine concentrations were highest after application to the neck and stifle. Transdermal application of 90 μg kg<sup>-1</sup> to the neck significantly (p < 0.05) increased thermal nociceptive thresholds from 3 hours and up to 36 hours after application. This corresponded with plasma buprenorphine concentrations ≥ 0.1 ng mL<sup>-1</sup>. Changes in locomotor activity, heart rate and borborygmi were minimal.</p><p><strong>Conclusions and clinical relevance: </strong>A thermal antinociceptive effect was observed after the transdermal delivery of 90 μg kg<sup>-1</sup> of buprenorphine, applied to the neck.</p>\",\"PeriodicalId\":23626,\"journal\":{\"name\":\"Veterinary anaesthesia and analgesia\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary anaesthesia and analgesia\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1016/j.vaa.2025.08.035\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary anaesthesia and analgesia","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1016/j.vaa.2025.08.035","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
The impact of transdermal application site on pharmacokinetics and selected pharmacodynamics of buprenorphine in horses.
Objective: To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses.
Study design: Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study.
Animals: Six (study 1) and eight (study 2) horses, aged 3-14 years.
Methods: In study 1, horses were administered a single dose of buprenorphine (45 μg kg-1), applied to the neck, croup and stifle. Blood samples were collected at fixed time points and a skin biopsy taken at the final time point for buprenorphine concentration analysis. In study 2, horses were administered a single transdermal dose of buprenorphine (90 μg kg-1) applied to the neck (determined in study 1). Blood samples were collected and buprenorphine concentrations determined by liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis performed. Pre- and post-drug-related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Mixed effects analysis of variance comparisons were performed to assess differences in pharmacodynamic parameters between baseline and each time point.
Results: Plasma buprenorphine concentrations were highest after application to the neck and stifle. Transdermal application of 90 μg kg-1 to the neck significantly (p < 0.05) increased thermal nociceptive thresholds from 3 hours and up to 36 hours after application. This corresponded with plasma buprenorphine concentrations ≥ 0.1 ng mL-1. Changes in locomotor activity, heart rate and borborygmi were minimal.
Conclusions and clinical relevance: A thermal antinociceptive effect was observed after the transdermal delivery of 90 μg kg-1 of buprenorphine, applied to the neck.
期刊介绍：
Veterinary Anaesthesia and Analgesia is the official journal of the Association of Veterinary Anaesthetists, the American College of Veterinary Anesthesia and Analgesia and the European College of Veterinary Anaesthesia and Analgesia. Its purpose is the publication of original, peer reviewed articles covering all branches of anaesthesia and the relief of pain in animals. Articles concerned with the following subjects related to anaesthesia and analgesia are also welcome:
the basic sciences;
pathophysiology of disease as it relates to anaesthetic management
equipment
intensive care
chemical restraint of animals including laboratory animals, wildlife and exotic animals
welfare issues associated with pain and distress
education in veterinary anaesthesia and analgesia.
Review articles, special articles, and historical notes will also be published, along with editorials, case reports in the form of letters to the editor, and book reviews. There is also an active correspondence section.
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