Dipivefrin and echothiophate: contraindications to combined use

Area of Science:

• Ophthalmology
• Pharmacology

Background:

• Dipivefrin is a prodrug converted to epinephrine, a potent ocular hypotensive agent.
• Cholinesterase inhibitors are used to treat glaucoma by increasing acetylcholine levels.

Purpose of the Study:

• To investigate if echothiophate iodide's antiesterase activity inhibits the conversion of dipivefrin to epinephrine.
• To assess the impact of this interaction on intraocular pressure (IOP) reduction.

Main Methods:

• Dipivefrin was administered to adult rabbits, both alone and in combination with echothiophate iodide.
• Intraocular pressure (IOP) was measured following drug administration under various treatment regimens.

Main Results:

• Dipivefrin alone significantly lowered IOP.
• Concomitant administration of echothiophate iodide with dipivefrin did not enhance IOP reduction compared to echothiophate alone.
• Adding epinephrine to eyes treated with dipivefrin and echothiophate resulted in further IOP decrease.
• When echothiophate was administered after dipivefrin, IOP returned to baseline levels.

Conclusions:

• The esterase responsible for converting dipivefrin to epinephrine appears to be inactivated by cholinesterase inhibitors like echothiophate iodide.
• The combined clinical use of cholinesterase inhibitors and dipivefrin may be contraindicated due to potential loss of efficacy.