The pharmacokinetics of tropic amide

Purpose: To develop a robust method for assessing pupil response to mydriatics and to assess the effect of age and prior instillation of proparacaine on the pharmacokinetics of tropicamide. Methods: Subjects were divided into two groups, according to age "younger" group (N=10, mean age 26yrs) and an "older" group (N=10, mean age 67 yrs). Subjects were excluded based on contact lens wear, ocular and systemic deases including dementia. Pupil response was tracked for 0.005%,0.01%, 0.05%, 0.1% and 0.5% tropicamide in a double blind experimental protocol. Experiments were separated by a minimum of 24 hours. Pupil dilation was measured using simultaneous photography of both eyes and a calibration scale. Photographs were taken prior to and following the installation of tropicamide into one eye and sterile saline into the fellow eye. Dilation with 0.5% tropicamide was also assessed with preinstillation of 0.25% proparacaine at varying times t=0 (drugs were mixed prior to instillation), 2.5, 5,7.5, 12.5 and 20 min, compared to 0.5% tropicamide alone.Results: Linear regression analysis showed constriction of the control pupil at all doses of tropicamide: 0.5% R=.996 (p<.001), 0.1% R=.979 (p<.001), 0.05% R=.342 (p<-001), 0.01% R=.260 (p<.005), 0.005% R=.430 (p<-05). Data fit with the Mechaelis-Menton function showed a compression of the dose response curve with age. Normalised curves showed maximal effect of proparacaine at a preinstillation time of 7.5 min, ss=10.99min±0.31 compared to no proparacaine ss=15.17min±0.75. The effect was comparable to the time course of anaesthesia. Conclusion: l)We devised a standard method for assessing mydriasis using anisocoria measurements and a correction factor for constriction of the control pupil. 2)Clinical implication of the compressed dose response curve to anticholinergic agents with age and the effects of proparacaine will be discussed.