Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits

As remdesivir, the first FDA-approved drug for SARS-CoV-2 infection, can be used only for hospitalized patients due to intravenous administration, there is an urgent need of effective oral antiviral formulations to be used at early stage of infection in an outpatient setting. The present paper reports on the comparative pharmacokinetics of the electrospun nanofiber remdesivir/sulfobutyl ether beta-cyclodextrin formulation after intravenous and buccal administration. It was postulated that oral transmucosal administration avoids remdesivir from metabolic transformation and intact remdesivir can be detected in plasma, but only the active metabolite GS-441524 could be experimentally detected at a significantly lower plasma level, than that provided by the intravenous route.

Highlights

• Fast-dissolving remdesivir/SBECD formulation obtained by electrospinning was studied.

• No intact remdesivir was detected after buccal administration to rabbits.

• Buccal administration resulted in much lower plasma levels of the metabolite than intravenous application.

In buccally treated animals, the metabolite GS-441524 appeared only at 1  h after treatment, while in intravenously treated animals, GS-441524 was possible to quantify even at the first time-point of blood collection. Further optimization of formulation is required to improve pharmacokinetics of remdesivir-sulfobutyl ether beta-cyclodextrin formulation upon buccal administration.

See the article here

Lajos Szente, Tibor Renkecz, Dávid Sirok, János Stáhl, Gábor Hirka, István Puskás, Tamás Sohajda, Éva Fenyvesi,
Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits, International Journal of Pharmaceutics, Volume 620, 2022, 121739, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.121739.