Di Cesare Federica, Gioeni Daniela, Ravasio Giuliano, Pellegrini Alberto, Lucatello Lorena, Bisutti Vittoria, Villa Roberto, Cagnardi Petra
Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy.
Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy.
J Vet Pharmacol Ther. 2019 Jul;42(4):392-400. doi: 10.1111/jvp.12771. Epub 2019 Jun 14.
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 μg/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 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 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.
本研究旨在确定右美托咪定和美沙酮经口腔黏膜途径或肌肉注射途径同时给药于犬时的药代动力学特征，并确定两种药物经口腔黏膜给药相对于肌肉注射给药的生物利用度，以及该给药途径在犬中的适用性。十二只预定进行诊断程序的客户拥有的犬，通过口腔黏膜途径或肌肉注射接受盐酸右美托咪定（10μg/kg）和盐酸美沙酮（0.4mg/kg）的联合治疗。口腔黏膜给药在大多数受试动物中引起流涎，肌肉注射引起短暂的外周血管收缩。结果显示，经口腔黏膜途径给药时，右美托咪定和美沙酮的吸收均减少且延迟，中位（范围）C值分别为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%。肌肉注射导致更有效的吸收情况，两种药物的AUC和C值大约高出10倍。使用注射用制剂经口腔黏膜途径同时给药的右美托咪定和美沙酮未很好地透过口腔黏膜吸收。尽管如此，建议对这些药物组合使用其他给药途径进行进一步研究。
