Comparison of the pharmacokinetics and sedative effects of Zenalpha (medetomidine and vatinoxan) administered intramuscularly and oral transmucosally in dogs

Abstract Objective To evaluate the sedative effects and pharmacokinetic profile of medetomidine and vatinoxan (Zenalpha) administered via the oral transmucosal (OTM) route. We hypothesized that sedation scores obtained from Zenalpha OTM (ZOTM) would not differ from Zenalpha IM (ZIM). Methods Dogs received 20 µg/kg ZIM or 80 µg/kg ZOTM. Sedation, anxiolytic, and handling scores were collected at 0, 15, 30, 30, 45, 60, 75, 90, 120, 150, and 180 minutes after administration of Zenalpha. Normality was tested using the Shapiro-Wilk test, and data were presented as median and range. Physiologic data were collected at 0, 5, 10, 15, 30, 45, 60, 90, 120, 240, 360, and 480 minutes. Plasma samples were collected at 0, 3, 5, 8, 8, 10, 15, 30, 45, 60, 90, 120, 240, 360, 480, 720, and 1,440 minutes and analyzed for concentration of medetomidine and vatinoxan using LC-MS-MS. Results 8 healthy adult Beagles participated in this study. Dogs in ZIM and ZOTM showed significant increases in sedation, anxiolysis, and handling scores compared to baselines. Medetomidine OTM was associated with a time to maximum concentration and relative bioavailability of 86 minutes (6 minutes ZIM) and 26.4%, respectively. Vatinoxan OTM was associated with a time to maximum concentration and relative bioavailability of 216 minutes (15 minutes ZIM) and 55.2%, respectively. Conclusions ZOTM (80 μg/kg) provided effective sedation, anxiolysis, and improved handling in healthy dogs comparable to ZIM (20 μg/kg) administration. Clinical Relevance Zenalpha administered OTM, at higher doses, may provide an attractive alternative to IM injection to achieve similar sedation.