Clinical pharmacokinetics of a dexmedetomidine-methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration
Clinical pharmacokinetics of a dexmedetomidine-methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration
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DOI：
10.1111/jvp.12771
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发表时间：
2019-07-01
影响因子：
1.3
通讯作者：
Cagnardi, Petra
中科院分区：
文献类型：
--
作者：
Di Cesare, Federica;Gioeni, Daniela;Cagnardi, Petra
本研究旨在确定右美托咪定和美沙酮同时经口给药和肌肉给药在犬体内的药动学特征，并确定两种药物经粘膜给药和肌肉给药的生物利用度，以及该给药途径在犬体内的适用性。12只客户所有的狗，计划进行诊断程序，通过口服粘膜途径或肌肉注射盐酸右美托咪定(10mgg/kg)和盐酸美沙酮(0.4mgkg)的组合进行治疗。口服经粘膜给药在大多数受试者中引起咳嗽，肌肉内给药引起一过性外周血管收缩。结果表明，右美托咪定和美沙酮经口腔粘膜给药后吸收均减少和延迟，C-max中位数分别为0.82(0.42-1.49)ng/ml和13.22(2.80-52.30)ng/ml。相对生物利用度较低：右美托咪定为16.34%，美沙酮为15.5%。肌肉内给药导致更有效的吸收曲线，两种药物的AUC和C-max值大约高出10倍。右美托咪定和美沙酮同时通过口腔粘膜给药，使用注射制剂，不能很好地被口腔粘膜吸收。然而，建议对使用替代给药途径的这些药物组合进行更多研究。
This study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client-owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 mu g/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) C-max values of 0.82 (0.42-1.49) ng/ml and 13.22 (2.80-52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and C-max values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended.