Aceclidine

Aceclidine is a cholinergic muscarinic agonist that stimulates muscarinic receptors located on smooth muscles. Aceclidine is a predominately pupil selective miotic that interacts with the iris with minimal ciliary muscle stimulation. Aceclidine causes contraction of the iris sphincter muscle, resulting in a pinhole effect that extends depth of focus to improve vision.

Aceclidine undergoes hydrolysis in the eye to acetate and 3-quinuclidinol (3-Q) with one mole of aceclidine hydrolyzed to one mole of 3-Q. Pharmacokinetic studies are performed on the analysis of 3-Q, which is a metabolite formed from the hydrolysis of aceclidine.

Systemic exposure of aceclidine hydrochloride was evaluated in 16 subjects with presbyopia following once daily aceclidine administration (one drop of aceclidine in each eye followed by a second drop in each eye two minutes later) for 8 days. The mean C_max and AUC_0-t values for 3-Q after Day 8 dosing were 2.114 ng/mL and 4.899 hr*ng/mL, respectively.

There was little to no accumulation of 3-Q after repeat once daily dosing of aceclidine. After 8 days, the mean (SD) RAUC_0-t and RC_max values were 1.189 (0.770) and 0.996 (0.314), respectively. T_1/2 could not be estimated at any timepoint due to the limited amount of quantifiable 3-Q concentrations after ocular dosing.