Improving the therapeutic index of topical phenylephrine by reducing drop volume

This study examined the effect of reducing eyedrop volume on the efficacy and systemic absorption of a given quantity of phenylephrine hydrochloride. Aqueous phenylephrine hydrochloride (2.5%) given in the commercially available drop volume of 32 microliters was compared with 10% aqueous phenylephrine given in an 8-microliters volume. Both preparations contained the same total amount of phenylephrine per drop. Ten subjects had both eyes dilated with each of the phenylephrine solutions according to a randomized, double-crossover sequence. The mean final pupillary diameter was nearly 1.0 mm larger for the 8-microliters drop (P = 0.0033). Nine of ten subjects achieved a larger pupillary diameter with the 8-microliters drop. Systemic absorption, as measured by plasma phenylephrine level, was similar for the two drop volumes. Thus, the 8-microliters drop achieved a significantly larger pupillary dilation without an increase in systemic absorption. Phenylephrine may have the most favorable risk-benefit ratio when administered as a high concentration in a small volume.