Vol. 28, Issue 12, 1394-1396, December 2000

SHORT COMMUNICATION
Increased Absorption of the Antiviral Ester Prodrug Tenofovir Disoproxil in Rat Ileum by Inhibiting Its Intestinal Metabolism

Jan Van Gelder, Sven Deferme, Pieter Annaert, Lieve Naesens, Erik De Clercq, Guy Van den Mooter, Renaat Kinget, and Parick Augustijns

Laboratorium voor Farmacotechnologie
en Biofarmacie,
Campus Gasthuisberg O&N,
Katholieke Universiteit,
Leuven, Belgium
(J.V., S.D., P.An., G.V., R.K., P.Au.);
Rega Institute for
Medical Research,
Katholieke Universiteit,
Leuven, Belgium
(L.N., E.D.)

Previous studies have shown that strawberry extract increases the transepithelial transport of tenofovir disoproxil, an esterase-sensitive prodrug of the antiviral compound tenofovir (formerly PMPA), across Caco-2 monolayers. This increase in transport was at least partially due to inhibition of its intestinal metabolism. To further study the feasibility of this absorption enhancing strategy, the influence of various concentrations of strawberry extract (0-2%) on the intestinal absorption of tenofovir disoproxil (100 µM) was assessed using an in situ perfusion model with immediate blood sampling from the mesenteric vein, a model closer to the in vivo situation than the in vitro Caco-2 system. Inclusion of strawberry extract (1%) resulted in a 7-fold increase in the appearance of tenofovir equivalents. The metabolism of tenofovir disoproxil in the intestinal perfusate was significantly lower in the presence of strawberry extract (1%), showing that the metabolism of tenofovir disoproxil is reduced by the flavoring extract.