Plasma pharmacokinetics of pilocarpine in participants administered VUITY^TM (pilocarpine HCl ophthalmic solution) 1.25%

Abstract

Purpose : Presbyopia is an age-related condition in which the eye exhibits a diminished ability to focus on near objects. VUITY^TM (pilocarpine HCl ophthalmic solution) 1.25% was recently approved in the US as the first and only prescription eye drop to treat presbyopia. The purpose of this study was to evaluate the systemic pharmacokinetics (PK) of pilocarpine following once daily administration of VUITY for 30 days.

Methods : Steady-state systemic PK of pilocarpine was assessed in 22 participants following bilateral, once-daily topical ocular administration of VUITY for 30 days. PK samples were collected on Day 1 at predose and on Day 30 at predose and 0.25, 0.5, 1, 3, 6, 8, and 10 hours postdose. Plasma concentrations of pilocarpine were quantified using a validated liquid-chromatography mass spectrometry (LC-MS/MS) method with an assay range of 25-5000 pg/mL and PK parameters were calculated using standard non-compartmental analysis methods.

Results : Pilocarpine was rapidly absorbed into systemic circulation with a median T_max,ss of 0.334 hours. Plasma concentrations of pilocarpine were measurable in most participants up to 8 to 10 hours postdose. The systemic exposure at steady state was low with mean C_max,ss and AUC_0-t,ss of 1950 pg/mL and 4140 pg^.hr/mL, respectively. The mean T_1/2 following 30 days of dosing was 1.74 hours. For most participants, C_trough,ss was below the assay LLOQ (< 25 pg/mL), indicating a lack of systemic accumulation of pilocarpine. Systemic exposure to pilocarpine following administration of VUITY for 30 days was lower than the exposure reported for other pilocarpine products available on the market. Mean plasma C_max and AUC_0-6hr achieved with VUITY were approximately 2 times lower than steady-state exposure reported after topical ocular administration of 4% Isopto Carpine. C_max achieved with VUITY was 21 times lower than the exposure reported with oral use of 10 mg Salagen.

Conclusions : Systemic exposure in participants administered VUITY once daily for 30 days was low and rapidly cleared from the circulation. Plasma concentrations were lower than those reported for other pilocarpine products on the market.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.