Alkalinization increases penetration of lidocaine across the human cornea

To test the hypothesis that corneal permeability of lidocaine complies with the principle of nonionic diffusion.

Department of Ophthalmology and Institute of Pharmacology, Vienna, Austria.

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 14C-labeled lidocaine across the tissue, measured at 15-minute intervals for 180 minutes, and corrected for the unidirectional fluxes of 3H-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.

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 <.002). The corneal content of lidocaine in the steady state was 65% higher at pH 7 than at pH 5 (2.8 +/- 0.9 micromol/cornea versus 1.7 +/- 1.2 micromol/cornea; not significant).

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.