Alkalinization increases penetration of lidocaine across the human cornea.

Abstract Purpose: To test the hypothesis that corneal permeability of lidocaine complies with the principle of nonionic diffusion. Setting: Department of Ophthalmology and Institute of Pharmacology, Vienna, Austria. Methods: Human corneas, mounted in an in vitro perfusion system under short-circuit conditions, were exposed on the epithelial (tear) side to lidocaine 4% in a buffered solution of pH 5 or pH 7. The endothelial bathing solutions had a constant pH of 7.4. Both solutions were adjusted to an osmolarity of 290 mOsm/L. The lidocaine permeability of the isolated corneas was assessed from the fluxes of 14 C-labeled lidocaine across the tissue, measured at 15-minute intervals for 180 minutes, and corrected for the unidirectional fluxes of 3 H-polyethylene glycol, a marker for the extracellular pathway. The corneal tissue content of lidocaine was estimated from the time span until the unidirectional lidocaine fluxes across the cornea reached a steady state. Results: The mean transcorneal fluxes of lidocaine in the steady state (90 to 180 minutes) were 72% higher at pH 7 than at pH 5 (101 mmol/min ± 37 (SD) versus 59 ± 34 nmol/min·cornea; P Conclusions: A shift in solution pH from 5 to 7 significantly increased the corneal permeability of topically applied lidocaine. Alkaline pH-adjustment of topical lidocaine solutions is easy to perform by adding sodium bicarbonate. The main clinical advantages of anesthetic solutions buffered at pH 7 are increased penetration rates, effectiveness, prolonged action time, and a reduction in local irritation and lacrimation.