摘要
目的考察口腔局部麻醉反转剂甲磺酸酚妥拉明注射液在健康人体的药代动力学(PK)特征。方法16例受试者随机分入上前牙粘膜下浸润麻醉组(A组)和下牙槽神经阻滞麻醉组(B组),每组8例,分3个周期依次接受0.90mL、1.80mL、3.60mL的2%盐酸利多卡因+1∶100 000肾上腺素进行局部麻醉,30min后在同一部位按照局麻药的相同给药方法,依次注射甲磺酸酚妥拉明注射液0.20mg、0.40mg、0.80mg,于每周期注射前5min至注射后15h中16个时点各采静脉血3mL,采用超高效液相色谱-质谱/质谱法(UPLC-MS/MS),以d4-盐酸酚妥拉明为内标(IS),测定血浆中酚妥拉明的浓度,采用非房室模型计算PK参数。观察不良事件,评估试验用药物的安全性。结果各剂量组均于注射后12～13min达峰浓度,不同部位局部给药的体内过程基本没有差异,可将其视为相同的口腔局部给药方式,峰浓度(C_(max))、0到t时间曲线下面积(AUC_(0-t))、0到无穷大时间曲线下面积(AUC_(0-∞))均随给药剂量成比例增加,半衰期为3.84～4.07h,清除率(CL)约为190L/h,甲磺酸酚妥拉明注射液在0.20～0.80mg剂量范围内基本具有线性动力学特征。不良事件主要为注射部位疼痛、头晕、心悸等,均为轻度。结论甲磺酸酚妥拉明注射液C_(max)、AUC_(0-t)、AUC_(0-∞)均具有线性动力学特征,安全性良好,值得口腔科临床推广应用。
Objective To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers. Methods A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate （16 time points）. Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters. Results Time to peak concerntration （tmax） ranged from 12 to 13 min. Half-time of elimination （t1/2） ranged from 3.84 to 4.07 h, with a clearance （CL） of 190 L/h. Peak concentration （Cmax）, area under concentration-time curves from 0 to t hour and from 0 to infinite time （AUC0-t and AUC0-∞） increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments. Conclusion Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.
作者
林诗蓓蕾
胡超
秦永平
苗佳
冯仕银
舒世清
南峰
王颖
朱晓红
梁茂植
LIN Shi-bei-lei;HU Chao;QIN Yong-ping;MIAO Jia;FENG Shi-yin;SHU Shi-qing;NAN Feng;WANG Ying;ZHU Xiao-hong;LIANG Mao-zhi(Phase Ⅰ Clinical Research Unit,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2018年第6期929-933,954,共6页
Journal of Sichuan University(Medical Sciences)
