Berke Kara, KuKanich Butch, Orchard Ron, Rankin David, Joo Hyun
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Department of Anatomy and Physiology and the Institute of Computational Comparative Medicine, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Vet Anaesth Analg. 2019 Nov;46(6):745-752. doi: 10.1016/j.vaa.2019.06.007. Epub 2019 Jul 17.
To evaluate drug interactions between fluconazole and the intravenous (IV) anesthetic induction agents, ketamine and midazolam.
Randomized parallel study.
A group of 12 adult healthy Beagle dogs.
Dogs were randomly allocated to two groups of six dogs. Dogs in group KM were administered IV ketamine (7 mg kg) and IV midazolam (0.25 mg kg), and dogs in group KMF were administered fluconazole (5 mg kg) orally 12 and 24 hours prior to ketamine-midazolam using the same doses as KM. Sedation scores (0-4) were assigned by investigators unaware of group assignment. Heart rate (HR) and times to sternal and standing were obtained and compared between groups for differences with p < 0.05 considered statistically significant. Blood was obtained and plasma drug concentrations were measured using liquid chromatography-mass spectrometry.
The times to sternal, mean 32.3 and 24.6 minutes, for groups KMF and KM, respectively, were not different between the groups. The time to standing, 73 and 36 minutes in groups KMF and KM, respectively, was significantly different (p = 0.002). The duration of elevated HR compared with baseline was longer in KMF (110 minutes) than in KM (25 minutes) (p < 0.05). In group KMF, one dog developed hyperthermia (40.6 °C), which resolved spontaneously. The clearance of ketamine and midazolam was significantly slower (approximately 50%) and the area under the curves were significantly higher (two-fold) in group KMF (p = 0.02).
A significant interaction between oral fluconazole and IV ketamine-midazolam occurred, but the effects appear minor in healthy dogs. Based on these data, a single dose of ketamine-midazolam is not contraindicated in dogs treated with fluconazole, but the duration of effects and pharmacokinetics are altered.
评估氟康唑与静脉麻醉诱导剂氯胺酮和咪达唑仑之间的药物相互作用。
随机平行研究。
一组12只成年健康比格犬。
将犬随机分为两组，每组6只。KM组犬静脉注射氯胺酮（7mg/kg）和咪达唑仑（0.25mg/kg），KMF组犬在使用与KM组相同剂量的氯胺酮和咪达唑仑前12小时和24小时口服氟康唑（5mg/kg）。由不知道分组情况的研究人员进行镇静评分（0 - 4分）。记录心率（HR）以及达到胸骨支撑位和站立位的时间，并比较两组之间的差异，p < 0.05被认为具有统计学意义。采集血液，使用液相色谱 - 质谱法测量血浆药物浓度。
KMF组和KM组达到胸骨支撑位的时间分别为平均32.3分钟和24.6分钟，两组之间无差异。KMF组和KM组达到站立位的时间分别为73分钟和36分钟，差异有统计学意义（p = 0.002）。与基线相比，KMF组心率升高的持续时间（110分钟）比KM组（25分钟）更长（p < 0.05）。在KMF组中，一只犬出现高热（40.6℃），随后自行消退。KMF组中氯胺酮和咪达唑仑的清除率显著减慢（约50%），曲线下面积显著升高（两倍）（p = 0.02）。
口服氟康唑与静脉注射氯胺酮 - 咪达唑仑之间存在显著相互作用，但在健康犬中这种影响似乎较小。基于这些数据，对于接受氟康唑治疗的犬，单次剂量的氯胺酮 - 咪达唑仑并非禁忌，但作用持续时间和药代动力学发生了改变。
