Kim Ju Hee, Kang Dong Wook, Choi Go-Wun, Lee Sang Bok, Lee Seongjin, Cho Hea-Young
College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea.
CHA Meditech Co., Ltd., Daejeon-si 1646, Korea.
Pharmaceutics. 2021 Feb 2;13(2):203. doi: 10.3390/pharmaceutics13020203.
Lidocaine-incorporated hyaluronic acid injection (LHA) is considered a promising way to increase patient compliance. Various reviews and analyses have been conducted to verify that the addition of lidocaine had no effect on the product quality of hyaluronic acid injections. However, possible pharmacokinetic (PK) alterations of lidocaine and its active metabolites, monoethylglycylxylidide (MEGX) and glycylxylidide (GX), in hyaluronic acid injection have not been studied so far. Thus, the objective of this study was to evaluate lidocaine and its metabolite PK after 0.3% lidocaine solution or LHA injection and to investigate any changes in PK profiles of lidocaine and its active metabolites. To do this, a novel bio-analytical method for simultaneous determination of lidocaine, MEGX, and GX in rat plasma was developed and validated. Then, plasma concentrations of lidocaine and its active metabolites MEGX and GX following subcutaneous (SC) injection of 0.3% lidocaine solution or LHA with 0.3-1% lidocaine in male Sprague-Dawley rats were successfully determined. The obtained data were used to develop a parent-metabolite pharmacokinetic (PK) model for LHA injection. The half-life, dose-normalized C, and AUC of lidocaine after SC injection of lidocaine solution and LHA did not show statistically significant difference. The PK characteristics of lidocaine after LHA administration were best captured using a two-compartment model with combined first-order and transit absorption and its clearance described with Michaelis-Menten and first-order elimination kinetics. Two one-compartment models were consecutively added to the parent model for the metabolites. In conclusion, the incorporation of lidocaine in hyaluronic acid filler injection did not alter the chemical's pharmacokinetic characteristics.
利多卡因复合透明质酸注射液（LHA）被认为是提高患者依从性的一种有前景的方法。已经进行了各种综述和分析，以验证添加利多卡因对透明质酸注射液的产品质量没有影响。然而，迄今为止，尚未研究利多卡因及其活性代谢物单乙基甘氨酰二甲苯酰胺（MEGX）和甘氨酰二甲苯酰胺（GX）在透明质酸注射液中可能的药代动力学（PK）改变。因此，本研究的目的是评估0.3%利多卡因溶液或LHA注射后利多卡因及其代谢物的PK，并研究利多卡因及其活性代谢物PK曲线的任何变化。为此，开发并验证了一种同时测定大鼠血浆中利多卡因、MEGX和GX的新型生物分析方法。然后，成功测定了雄性Sprague-Dawley大鼠皮下（SC）注射0.3%利多卡因溶液或含0.3-1%利多卡因的LHA后利多卡因及其活性代谢物MEGX和GX的血浆浓度。所获得的数据用于建立LHA注射的母体-代谢物药代动力学（PK）模型。皮下注射利多卡因溶液和LHA后，利多卡因的半衰期、剂量标准化的C和AUC没有显示出统计学上的显著差异。LHA给药后利多卡因的PK特征最好用具有一级和转运吸收组合的二室模型来描述，其清除率用米氏和一级消除动力学来描述。在母体模型中连续添加两个一室模型来描述代谢物。总之，在透明质酸填充剂注射中加入利多卡因不会改变该化学物质的药代动力学特征。
