Systemic side effects of eye drops: a pharmacokinetic perspective

Abstract

When administering eye drops, even when completely correctly applied, several routes of absorption are possible and excess amounts can sometimes cause an unwanted systemic bioavailability of the drops when not completely absorbed into the eye. Furthermore, the concentration of active ingredients in such medicinal preparations is usually very high, so that despite the correct application of the recommended dose, considerable amounts may be absorbed in an unwanted manner through various routes. Children are subject to a much higher risk of systemic side effects because ocular dosing is not weight adjusted and physiological development (eg, liver status) differs from that of adults. There is a lack of information about pediatric dosing in the current literature. This review summarizes the most important clinically relevant systemic side effects that may occur during ophthalmic eye treatments. In this review, we discuss general pharmacokinetic considerations as well as the advantages, disadvantages, and consequences of administering drugs from some important drug groups to the eye.

High-precision piezo-ejection Ocular microdosing: Phase II Study on Local and Systemic Effects of Topical Phenylephrine

“…Absorption of topical ocular drugs into the general circulation is associated with diverse AEs that are occasionally serious [8,23,24], and PE is not exempted [25,26]. PE is similar to epinephrine/norepinephrine in chemical structure and also has cardiovascular activity.…”

Common eye infections

“…However, the risk of systemic absorption is low since ocular drug bioavailability is 5-10% and the corneal epithelium and conjunctival epithelium act as natural barriers limiting absorption. 28 Some adverse effects include skin irritation, itching or rash with sulfonamide, sulfacetamide and neomycin. 28 Fluoroquinolones can cause local irritation, stinging, chemosis, conjunctival hyperaemia, corneal precipitations and alteration of taste.…”

“…28 Some adverse effects include skin irritation, itching or rash with sulfonamide, sulfacetamide and neomycin. 28 Fluoroquinolones can cause local irritation, stinging, chemosis, conjunctival hyperaemia, corneal precipitations and alteration of taste. 29 A minimal dose and concentration of the antibiotic must be used in pregnancy to limit systemic absorption.…”

Delivery of therapeutics for deep-seated ocular conditions – status quo

“…[12] Depending on the therapeutic drug, this mechanism can increase systemic adverse effects ranging from hypotension and bradycardia in timolol to palpitations and headaches in adrenaline eye drops, especially in paediatric and elderly cohorts. [13,14] In addition to conjunctival and lacrimal drainage into the nasal cavity, the drug absorption into the conjunctiva, lacrimal ducts, and nasal cavity also accounts for a significant loss of precorneal drug bioavailability, with absorption from the nasal mucosa contributing to the most drug absorption. [15] This is particularly a problem considering the limited permeability of the cornea.…”

“…[3][4][5][6][7] -Collectively, these barriers contribute to why topically instilled drug is typically washed away in 15-40 s. [8,9] Conjunctiva and nasal absorption of drug -Significant drug absorption into the conjunctiva and nasal cavity results in systemic adverse drug effects. [12][13][14] -More importantly, it acts to decrease the drug concentration at the corneal absorptive membrane resulting in low transcorneal penetration. [15][16][17] Corneal epithelium barrier -The epithelial layer of the cornea is the rate-limiting barrier for most transcorneal penetration.…”