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Pharmacokinetics of midazolam and its major metabolite 1-hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations.
Journal of Veterinary Pharmacology and Therapeutics ( IF 1.5 ) Pub Date : 2019-08-30 , DOI: 10.1111/jvp.12806
Cédric B Larouche 1, 2 , Ron Johnson 3 , Francis Beaudry 4 , Craig Mosley 5 , Yu Gu 3 , Kristopher Afshaun Zaman 1 , Hugues Beaufrère 6 , Christopher Dutton 2
Affiliation  

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1-hydroxymidazolam were determined by the use of high-performance liquid chromatography tandem-mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half-lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration-time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady-state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr-1 kg-1 , and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1-hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1-hydroxymidazolam following IC administration.

中文翻译:

心脏内和肌肉内给药后,球蟒(Python regius)中咪达唑仑及其主要代谢物1-羟基咪达唑仑的药代动力学。

咪达唑仑是一种苯二氮卓类药物,具有镇静,肌肉松弛,抗焦虑和抗惊厥作用。在一项平行研究中,使用十二个球蟒(Python regius)评估了单次心内(IC)或肌内(IM)给药后1 mg / kg咪达唑仑的药代动力学。从给药前7天开始或直到给药72小时后的15个时间点,从放置7天或通过心脏穿刺的中央静脉导管收集血液。使用高效液相色谱串联质谱法测定咪达唑仑和1-羟基咪达唑仑的血浆浓度,并使用非房室分析法估算药代动力学参数。IC和IM咪达唑仑的平均±SD末端半衰期分别为12.04±3.25小时和16.54±7.10小时。浓度-时间曲线下推断出的咪达唑仑稳定状态下的无穷大,清除率和稳态表观分布体积的面积分别为19112.3±309.5 ng * hr / ml,0.053±0.008 L hr-1 kg-1和0.865±分别为0.289 L / kg。IM咪达唑仑的生物利用度估计为89%。IM给药后,咪达唑仑和1-羟基咪达唑仑在注射后分别达到2.33±0.98小时和24.00±14.12hr的最大血浆浓度,IC给药后,1-羟基咪达唑仑在注射后达到22.33±20.26小时。
更新日期:2019-11-01
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