Effect of Age and Viscosity on Duration of Corneal Anesthesia with Topical 2% Lidocaine Administration

Formulation viscosity and patient-specific parameters such as age are important considerations in achieving patient comfort for prolonged anterior segment surgical procedures. In this study, we report pharmacodynamic and pharmacokinetic parameters of topical 2% lidocaine anesthetic decay based on formulation viscosity and subject age. Extemporaneous 2% lidocaine solution was compounded with varying percentages of carboxymethylcellulose (CMC) to adjust product viscosity. Juvenile and adult New Zealand White rabbits were utilized as a model for lidocaine-induced corneal anesthesia analysis. Following application of 20 μL in 1 eye of each animal, corneal sensitivity was measured using a Cochet-Bonnet esthesiometer at baseline and at 1-min intervals until recovery to baseline. Subsequent to washout period, the experiment was repeated for 3 replicate experiments. A one-phase exponential decay model was utilized to describe rate of anesthesia decay. Bioavailability increased in a manner disproportionate to both tear film concentration and solution viscosity. In adult animals, half-life of anesthetic decay was found to range from 6.03 min with 2% lidocaine in 0.5% CMC to 9.45 min with 2% lidocaine in 1.5% CMC. In juveniles, half-life was found to be 4.46 and 3.58 min for 2% lidocaine in 1.5% CMC and commercial 2% lidocaine gel, respectively. Decay parameters of lidocaine-induced corneal anesthesia appear disparate from viscosity. It is postulated that viscosity-related increase in corneal contact time through reduced drainage plays a critical role in increasing bioavailability of topical anesthetics in our experimental findings, although nonlinear in character. Age is found to be an important mediator of lidocaine-induced corneal anesthesia.