Menczel E, Yacobi A, Paran I, Lustig A
Arch Int Pharmacodyn Ther. 1977 Feb;225(2):330-42.
The pH partition hypothesis was applied to the absorption of ionizable local anesthetic amines through the subcutaneous (s.c.) route. Solutions of lidocaine hydrochloride (LHCl), procaine hydrochloride (PHCl) and tetracaine hydrochloride (THCl) at various pH were implanted on s.c. animal tissue through a glass absorption cell. The s.c. absorption of these drugs was evaluated from the clearances' slopes evolved by determination of the drugs' concentrations in the cell at definite intervals. The higher the pH level, these conjugated bases become more unionized and lipid partitioned resulting in increased rates of s.c. absorption. The extent of unionization is governed by the pka of each of these drugs; at the high feasible pH--procaine which is least unionized--its s.c. absorption rate is nearly a third of that of lidocaine or tetracaine. The pH effect on s.c. absorption of local anesthetics was substantiated by estimation of lethal time50 (LT50) in mice.
pH分配假说被应用于可电离局部麻醉胺类药物经皮下途径的吸收研究。将不同pH值的盐酸利多卡因（LHCl）、盐酸普鲁卡因（PHCl）和盐酸丁卡因（THCl）溶液通过玻璃吸收池植入动物皮下组织。通过在特定时间间隔测定吸收池中药物浓度得出的清除率斜率来评估这些药物的皮下吸收情况。pH值越高，这些共轭碱的非离子化程度越高，脂溶性越强，导致皮下吸收速率增加。非离子化程度由每种药物的pKa决定；在高可行pH值下，普鲁卡因的非离子化程度最低，其皮下吸收速率几乎是利多卡因或丁卡因的三分之一。通过估计小鼠的半数致死时间（LT50），证实了pH值对局部麻醉药皮下吸收的影响。
