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.

药物处方的个体化已成为当前药理学研究的热点，旨在尽可能降低药物的副作用。现有文献中的某些研究揭示了细胞色素P450多态性，尤其是CYP3A4和CYP1A2，对利多卡因代谢为其主要代谢产物单乙基甘氨酰基哌啶（MEGX）的影响。利多卡因是全球牙科领域最常用的局部麻醉剂，也是市场上历史最悠久的钠通道阻滞剂之一，被认为是最安全的酰胺类局部麻醉剂。即便如此，它仍可能对心血管系统和中枢神经系统产生一些副作用，尤其是当药物意外直接注入血管时。与血管收缩剂，尤其是肾上腺素的联合使用，是减少这些副作用的一种策略。在本研究中，将根据研究方案，在前18个月内收集尽可能多的志愿者的临床数据，他们将在两次不同的牙科预约中接受治疗，包括刮治和牙冠-根管抛光，以及在上颌磨牙区域使用含或不含有1:100,000肾上腺素的利多卡因胶囊进行牙袋浸润注射。对于药代动力学（PK）研究，将收集唾液样本。对于药效学参数（PD），在手术过程中将评估血压、血氧饱和度和心率的变化，以及软组织局部麻醉的开始时间和持续时间。总之，将对CYP3A4和CYP1A2多态性及其与个体患者反应的关系进行分析。