Aqueous penetration of oral and topical indomethacin in humans

Aqueous humor and serum indomethacin levels were determined following administration of the drug orally, as a topical 1% aqueous suspension and as a topical 1% oil suspension. Patients receiving indomethacin orally had a mean aqueous humor level below the lower limit of sensitivity of the assay, which is also below the level known to inhibit prostaglandin synthesis in vitro and a mean serum level of 642 ng/mL. Patients receiving the topical 1% aqueous suspension had a mean aqueous level of 198 ng/mL and no detectable serum level. Patients receiving the topical 1% oil suspension had a mean aqueous level of 429 ng/mL, which was significantly higher than that of the aqueous suspension. Both topical suspensions yield levels that are able to inhibit prostaglandin synthesis. Higher aqueous levels with no detectable blood levels (and thus negligible potential for systemic toxic effects) make the topical route of administration preferable to the oral route.