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The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.5 ) Pub Date : 2020-02-03 , DOI: 10.1111/jvp.12838
Stuart W Paine 1 , Jane Bright 2 , James P Scarth 2 , Pamela R Hincks 2 , Clive M Pearce 2 , Colette Hannan 3 , Marc Machnik 4 , Lynn Hillyer 5
Affiliation  

In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentrations of butorphanol, detomidine and 3-hydroxydetomidine at predetermined time points were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The intravenous pharmacokinetics of butorphanol dosed individually compared with co-administration with detomidine had approximately a twofold larger clearance (646 ± 137 vs. 380 ± 86 ml hr-1 kg-1 ) but similar terminal half-life (5.21 ± 1.56 vs. 5.43 ± 0.44 hr). Pseudo-steady-state urine to plasma butorphanol concentration ratios were 730 and 560, respectively. The intravenous pharmacokinetics of detomidine dosed as a single administration compared with co-administration with butorphanol had similar clearance (3,278 ± 1,412 vs. 2,519 ± 630 ml hr-1 kg-1 ) but a slightly shorter terminal half-life (0.57 ± 0.06 vs. 0.70 ± 0.11 hr). Pseudo-steady-state urine to plasma detomidine concentration ratios are 4 and 8, respectively. The 3-hydroxy metabolite of detomidine was detected for at least 35 hr in urine from both the single and co-administrations. Detection times of 72 and 48 hr are recommended for the control of butorphanol and detomidine, respectively, in horseracing and equestrian competitions.

中文翻译:

与单独剂量的运动马匹相比,丁苯啡诺和地托米定的静脉内药代动力学组合给药。

在马匹和竞速赛中,由于它们的镇静作用,常联合使用托托咪定和丁烷醇。这项研究的目的是确定检测时间,以便更好地为欧洲兽医提供信息,从而使两种药物都可以在监管规则下适当使用。三组分别为7、8和6匹马的独立组分别接受单次静脉注射布托啡诺(100 µg / kg),单次静脉注射地托米定(10 µg / kg)或两者的组合(25 mg) )和10(地托米定)µg / kg。通过液相色谱-串联质谱法(LC-MS / MS)在预定的时间点测量血浆中的吗啡醇,丁吗啡丁和3-羟基吗啡丁的血浆和尿液浓度。与共同使用地托咪定相比,单独使用的丁烷酚的静脉药代动力学清除率大约高两倍(646±137对380±86 ml hr-1 kg-1),但终末半衰期相似(5.21±1.56对5.43) ±0.44小时)。伪稳态尿液与血浆中的布托啡诺浓度比分别为730和560。与丁苯啡诺合用相比,单次给药的托托咪定的静脉药代动力学具有相似的清除率(3,278±1,412对,2,519±630 ml hr-1 kg-1),但终末半衰期略短(0.57±0.06 vs 0.70±0.11 hr)。伪稳态尿液与血浆托托咪定的浓度比分别为4和8。在单次给药和共同给药的尿液中,检测到了至少35个小时的异胃定的3-羟基代谢产物。
更新日期:2020-02-03
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