Intraocular and Systemic Pharmacokinetics of Triamcinolone Acetonide after a Single 40-mg Posterior Subtenon Application

Abstract

To characterize the pharmacokinetics of triamcinolone acetonide (TA) in aqueous, vitreous, and systemic circulation after a single subtenon injection. Prospective interventional case series. Thirty-six patients (36 eyes) who received a single posterior subtenon injection of TA (40 mg in 0.4 ml). Aqueous, vitreous, and blood samples were obtained at 1-hour, 1-day, 3-day, 5-day, 10-day, 14-day, 21-day, and 28-day time points after the posterior subtenon TA injection. At each time point, there were 3 to 6 eyes (patients). The concentrations of TA in the aqueous, vitreous, and plasma were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Triamcinolone acetonide concentration in the samples was measured, and pharmacokinetic parameters were calculated. The TA concentration-time profile in aqueous consisted of a fast distribution phase during the first 24 hours and a slow elimination phase thereafter. In contrast, the TA concentration-time profile in vitreous consisted of an absorption phase during the first 24 hours followed by a slow elimination phase. The TA in plasma followed a mono-exponential elimination during the study course. The TA concentration peak time for aqueous and plasma was at 1 hour and 24 hours, for vitreous after subtenon injection. The terminal elimination half-life in aqueous, vitreous, and plasma was 11.8, 17.1, and 25 days, respectively. The integral of the area under the concentration time curve (AUC(0-∞)) was 862 ng/day/ml for aqueous, 1262 ng/day/ml for vitreous, and 17.4 ng/day/ml for plasma. The total TA exposure to vitreous was 46% more than total TA exposure to the aqueous. The TA concentration in vitreous was 70- to 98-fold higher than that in plasma. Posterior subtenon TA application can provide a sustained high local ocular TA level while also resulting in a very low systemic TA level, which may be well below the normal glucocorticoid level in humans.