Pharmacogenetic and PK/PD study after infiltrative application of lidocaine associated or not with epinephrine in saliva samples by LC MS/MS

The individualization of drug prescription has increasingly become the focus of current research in pharmacology so that the adverse effects of drugs are minimized whenever possible. Some studies in the current literature show the relationship that cytochrome P450 polymorphisms, more specifically CYP3A4 and CYP1A2, exert on the metabolism of lidocaine into its main metabolite, monoethyl-glycinexylidide (MEGX). Lidocaine is the most used local anesthetic in dentistry worldwide, being one of the oldest sodium channel blockers on the market and considered the safest amide local anesthetic. Even so, it can cause some side effects on the cardiovascular system and the central nervous system, especially when accidental administration occurs directly into a blood vessel, and the association with vasoconstrictors, especially epinephrine, is a strategy to minimize these effects. In this research, clinical data will be collected from the largest possible number of volunteers in the first 18 months of the project, who will attend two different dental appointments, according to the protocol, for scaling and crown-radicular polishing, sulcular infiltrative injection in the region of maxillary molars of a cartridge of lidocaine associated or not with 1:100,000 epinephrine. For the pharmacokinetic (PK) study, saliva samples will be collected. For the pharmacodynamic parameters (PD), variations in blood pressure, oximetry, and heart rate will be evaluated during the procedure, in addition to the beginning and duration of local anesthesia in soft tissues. Altogether, data will be analyzed for CYP3A4 and CYP1A2 polymorphisms and their relationship with individual patient responses.药物处方个体化已日益成为当前药理学研究的热点方向，旨在尽可能将药物不良反应降至最低水平。现有文献中的多项研究证实，细胞色素P450（cytochrome P450）多态性——更具体为CYP3A4与CYP1A2——可影响利多卡因代谢为其主要代谢产物单乙基甘氨酰二甲苯胺（monoethyl-glycinexylidide, MEGX）的过程。 利多卡因是全球牙科临床应用最广泛的局部麻醉药，亦是市面上最老牌的钠通道阻滞剂（sodium channel blocker）之一，被公认为安全性最佳的酰胺类局部麻醉药。即便如此，其仍可能对心血管系统与中枢神经系统引发不良反应，尤其是当药物不慎直接注入血管时；而与血管收缩剂（尤其是肾上腺素）联用，正是降低此类风险的经典策略。 本研究将在项目启动后的前18个月内，招募尽可能多的志愿者收集临床数据。所有志愿者需按照试验方案完成两次牙科诊疗：其一为龈上洁治与根面抛光术，其二为上颌磨牙区域的龈沟浸润麻醉，注射使用1支含或不含1:100000肾上腺素的利多卡因cartridge。药代动力学（pharmacokinetic, PK）研究将采集唾液样本；药效动力学（pharmacodynamic, PD）参数评估则涵盖操作全程的血压、血氧饱和度与心率变化，同时记录局部软组织麻醉的起效时间与持续时长。最终将整合全部采集数据，针对CYP3A4与CYP1A2多态性及其与患者个体应答间的关联开展分析。