Department of Oral Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030, USA.
J Am Dent Assoc. 2012 Aug;143(8):872-80. doi: 10.14219/jada.archive.2012.0291.
The authors evaluated the cardiovascular effects and pharmacokinetics of an intranasal 3 percent tetracaine/0.05 percent oxymetazoline spray developed to provide needle-free anesthesia of maxillary teeth.
The authors administered to 12 participants a proposed maximum recommended dose (MRD) (18 milligrams tetracaine/0.3 mg oxymetazoline) as three bilateral pairs of 0.1-milliliter nasal sprays. They administered two times this dose (36 mg tetracaine/0.6 mg oxymetazoline) as six bilateral pairs one to three weeks later. The authors recorded the patients' heart rate, blood pressure and oxygen saturation. They drew blood samples at baseline and 15 times during the two hours after drug administration.
Physiological measures remained fairly stable throughout the two-hour period, with small but significant decreases (P < .05) in heart rate at 40 and 50 minutes for the two-times MRD (6.1 beats/minute) and MRD (7.5 beats/minute) administrations, respectively, and a significant increase in diastolic blood pressure (5.9 millimeters of mercury) for the two-times-MRD administration at 90 minutes. Mean oxygen saturation remained above 99 percent. Tetracaine plasma levels were undetectable in most participants, whereas concentrations of its major metabolite parabutylaminobenzoic acid from the two-times-MRD administration were approximately twice that from the MRD administration. Oxymetazoline concentrations from the two-times-MRD administration were approximately 50 percent greater than those from the MRD administration, with a half-life of 1.72 to 2.32 hours.
Intranasal tetracaine/oxymetazoline mist generally was well tolerated in study participants.
The safety profile and pharmacokinetics of this intranasal formulation indicate that it appears to be generally well tolerated in patients for achieving anesthesia of the maxilla. Additional safety and efficacy data are required, particularly in patients with cardiovascular disease and other comorbidities.
作者评估了一种用于上颌牙齿无针麻醉的 3% 丁卡因/0.05% 羟甲唑啉鼻喷雾剂的心血管效应和药代动力学。
作者给 12 名参与者使用了建议的最大推荐剂量（MRD）（18 毫克丁卡因/0.3 毫克羟甲唑啉），作为三次双侧 0.1 毫升鼻喷雾剂。三到一周后，他们给参与者使用两倍剂量（36 毫克丁卡因/0.6 毫克羟甲唑啉），作为六次双侧喷雾剂。作者记录了患者的心率、血压和血氧饱和度。他们在给药后两小时内的 15 次采血。
在两小时内，生理指标相对稳定，两次 MRD（分别为 6.1 次/分钟和 7.5 次/分钟）和 MRD（50 分钟时心率略有下降（P <.05），两次 MRD（90 分钟时舒张压升高 5.9 毫米汞柱）。平均血氧饱和度保持在 99%以上。大多数参与者的丁卡因血浆水平无法检测到，而两次 MRD 给药的其主要代谢物对丁基氨基苯甲酸的浓度约为 MRD 给药的两倍。两次 MRD 给药的羟甲唑啉浓度约为 MRD 给药的 50%，半衰期为 1.72 至 2.32 小时。
鼻内给予丁卡因/羟甲唑啉喷雾一般在研究参与者中耐受良好。
这种鼻内制剂的安全性概况和药代动力学表明，它似乎在患者中普遍耐受良好，可用于实现上颌麻醉。需要更多的安全性和疗效数据，特别是在患有心血管疾病和其他合并症的患者中。
