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 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. 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 <.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). 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.
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 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. 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 <.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). 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.
Authors: Agnieszka Gawin-Mikołajewicz; Karol P Nartowski; Aleksandra J Dyba; Anna M Gołkowska; Katarzyna Malec; Bożena Karolewicz Journal: Mol Pharm Date: 2021-09-17 Impact factor: 4.939