Ocular pharmacokinetic study of a corticosteroid by 19F MR

Abstract

Traditional ocular pharmacokinetic studies are invasive and cannot be easily applied to humans in vivo. To acquire in vivo ocular pharmacokinetic data noninvasively, (19)F MR on a 3T clinical scanner was used to follow the real time dynamics of a corticosteroid in the eye. (1)H MR was also performed to locate the site of administration. Triamcinolone acetonide phosphate (TAP) was the model drug, administered by intravitreal and subconjunctival injections. TAP pharmacokinetics were monitored by changes in the (19)F spectrum of the intraocular drug in real time. The elimination half-lives of TAP in the eye after intravitreal and subconjunctival injections were 8 and 0.5 h in vivo and 17 and 6.0 h postmortem, respectively. The half-lives associated with clearance were 14 h for intravitreal injection and 0.5 h for subconjunctival injection.

Fig. 1

Molecular structures of triamcinolone acetonide phosphate (left) and triamcinolone acetonide (right).

Fig. 2

Representative ¹⁹F spectra at (a) one time point and (b) different time points obtained in a rabbit in vivo, where all spectra have been normalized according to the KF spectrum. In (b), the time axis is not spaced according to the time scale.

Fig. 3

¹H MR images (a) right before, (b) immediately and (c) 5 h after the intravitreal injection. The bright region in (b) indicates the initial location of the TAP/MnEDTA/saline solution.

Fig. 4

Amount of TAP determined from TAP signal versus time after intravitreal injection in vivo and postmortem. The dotted line indicates the detection limit with the coil and pulse sequence used in this study.

Fig. 5

Amount of TAP determined from TAP signal versus time after subconjunctival injection in vivo and postmortem. The insert shows an enlarged view of the early in vivo data. The dotted line indicates the detection limit with the coil and pulse sequence used in this study.