Drug Metabolism Plays Only a Minor Role in Ocular Pharmacokinetics, Drug Elimination

Article: New data on drug metabolism and distribution in the eye
Source: University of Eastern Finland, Pharmacy (Finland)
Published: January 27, 2022

Ocular pharmacokinetics, the study of how the tissues in the eye process drugs, is an important aspect of drug discovery and development for ocular conditions, from treating the occasional eye infection and eye pain to eye diseases that require ongoing therapy such as glaucoma, diabetic retinopathy, and age-related macular degeneration. However, drug profiles as measured through hepatic metabolism do not accurately predict drug metabolism in the eye. Researchers in Finland conducted a quantitative assessment of four drugs and their metabolites in a rabbit eye model via intracameral and intravitreal administrations. The four drugs studied were acetaminophen (analgesic and antipyretic), brimonidine (IOP reduction), cefuroxime axetil (antibiotic), and sunitinib (anti-angiogenic). Data was collected from the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina. The authors report that secondary pharmacokinetic assessments—such as the area under the plasma drug concentration-time curve (AUC), which reflects the body's actual exposure to a drug after administration—were 12-70 times lower for metabolites than they were for the parent drug in eye tissues with the highest enzymatic activity. An exception was the ester prodrug cefuroxime axetil, which was efficiently converted to cefuroxime in ocular tissues. Furthermore, metabolic enzymes that are abundant in the liver were sparse in the eye, resulting in negligible ocular drug clearance. The researchers conclude that with the exception of esterase substrates, metabolism seems to play a minor role in ocular pharmacokinetics, that is, elimination was through non-metabolic processes such as through vascular, lacrimal, and aqueous fluid dynamics; nonetheless, they point out that drug metabolism in the eye merits further investigation in that accumulation of drugs or their metabolites could contribute to ocular toxicity.

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Del Amo EM, Hammid A, Tausch M, et al. "Ocular metabolism and distribution of drugs in the rabbit eye: Quantitative assessment after intracameral and intravitreal administrations." International Journal of Pharmaceutics.  613:121361. 5 February 2022. https://doi.org/10.1016/j.ijpharm.2021.121361