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Muhammad Abdulrazik; The merits of double label pharmacokinetics in ocular PK’s: evidence from a study of 3H-labeled drug and 14C-labeled vehicle. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4459.
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Vehicles can mask the physicochemical properties of active ingredients with poor penetration through ocular tissues and evaluation studies, of the extent of penetration and in vivo longevity of the assembled vehicle-drug pair, are used to develop a successful vehicle for this mission. The current study aims at investigating the merits of using two radioactive labels, for both drug and vehicle, in ocular pharmacokinetic studies.
A single 50 µl topical dose of 3H-labeled dexamethasone-palmitate 0.1%, formulated in 14C-labeled oil-in-water emulsion was administered to the cul-de-sac of one eye of albino rabbits (2-2.5 kg). At 15, 30, 45, 60, 120, 180 and 360 min. and 24 hrs. post dosing, 3H- and 14C- determinations were carried out in harvested ocular tissues of the euthanized animals (n=4 at each time point). Pearson correlation coefficients (R) were calculated for pairs of 3H- and 14C- determinations along the eight time points.
In the treated eye, significant positive correlation between 3H- and 14C- determinations (from 15 min. to 24 hrs.) was evidenced in main port of entry of the topical dose, the conjunctiva (R 0.867/ p 0.0053), in minor port of entry, the cornea (R 0.8803/ p 0.0039), and in sclera (R 0.7335/ p 0.0384), choroid (R 0.9705/ p 6.3E-05), retina (R 0.7668/ p 0.0264), lens (R 0.9165/ p 0.0014) and vitreous (R 0.7126/ p 0.0473), but not ciliary body (R 0.476/ p 0.2332), iris (R 0.341/ p 0.4085) and aqueous humor (R 0.6209/ p 0.1005). However, the correlation was strongly positive in those three sites when only later time points were considered (from 1 to 24 hrs.): ciliary body (R 0.9091/ p 0.0325), iris (R 0.9818/ p 0.0029) and aqueous humor (R 0.9274/ p 0.0232).
The best positive correlations between 3H- and 14C- determinations, across the studied time points and the sampled tissues, matched the expected route and extent of penetration of the assembled oil-in-water emulsion of dexamethasone palmitate after topical administration to the cul-de-sac of the albino rabbit eye. This confirmatory evidence is in support of using double label in ocular PK's, for both active ingredient and vehicle, when there is a need to investigate the extent of penetration and in vivo longevity of a drug and its vehicle as an assembled pair.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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