Menczel E, Goldberg S
Dermatologica. 1978;156(1):8-14. doi: 10.1159/000250891.
(1) The percutaneous penetration of lignocaine hydrochloride is affected in vitro by the pH; alkalinity increased the portion of the unionized drug which permeated through the lipoid outer skin membrane of guinea pigs. (2) The amount of lignocaine accumulated on the dermal side of the diffusion cell containing isotonic phosphate buffer (pH 7.4) was directly proportional to the initial concentration of the applied drug at the alkaline pH. (3) The dermal transfer rates of lignocaine into the isotonic phosphate buffer (pH 7.4) of the diffusion cell decreased with the increase in the pH of the initially applied solution on the epidermal side of the diffusion cell; the simultaneous cutaneous penetration of the alkaline buffer promoted retention of the unionized drug in the dermis. (4) Percutaneous penetration of lignocaine hydrochloride represents a dual-stage process involving dissimilar rates of clearance into cutaneous tissue and transfer from dermis to body fluids. Variations in the alkaline pH of lignocaine hydrochloride solution appear to govern the rate-limiting factor of the total percutaneous penetration; the pharmacologic action of lignocaine may thus be localized.
（1）盐酸利多卡因的经皮渗透在体外受pH值影响；碱性增强了透过豚鼠类脂性外皮膜渗透的非离子化药物的比例。（2）在含有等渗磷酸盐缓冲液（pH 7.4）的扩散池中，利多卡因在皮肤侧的累积量与碱性pH下所用药液的初始浓度成正比。（3）利多卡因向扩散池等渗磷酸盐缓冲液（pH 7.4）中的皮肤转运速率随扩散池表皮侧初始给药溶液pH值的升高而降低；碱性缓冲液同时经皮渗透促进了非离子化药物在真皮中的滞留。（4）盐酸利多卡因的经皮渗透代表一个双阶段过程，涉及进入皮肤组织的清除速率和从真皮到体液的转运速率不同。盐酸利多卡因溶液碱性pH的变化似乎决定了总经皮渗透的限速因素；因此，利多卡因的药理作用可能会局限化。
