Comparative subcutaneous absorption of local anesthetics: lidocaine, procaine and tetracaine.
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.
D000818:Animals; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D011343:Procaine / Q000378:metabolism* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D012869:Skin Absorption; D013748:Tetracaine / Q000378:metabolism* / Q000633:toxicity; D013997:Time Factors
D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine