Oral pharmacokinetic interaction of ester rich fruit juices and pharmaceutical excipients with tenofovir disoproxil fumarate in male Wistar rats

Abstract

1. The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF).

2. The esterase inhibition capacity of fruit juices (FJs) rich in ester linkages and pharmaceutical excipients (having ester bonds) was performed in vitro by incubating TDF with each FJ and excipient in the intestinal washings. The ex vivo everted gut sac model was also used to evaluate the absorption enhancement capacity of these FJs and excipients. Single-dose oral pharmacokinetic studies were performed by concomitant administration of TDF with each of the selected FJs and excipients.

3. The in vitro and ex vivo studies showed that cremophor-EL and all FJs prevented the metabolism of TDF with grapefruit juice (GFJ) having the highest level of inhibition. Further, the permeability flux of the monoester form of tenofovir was increased by 113% and 212% by cranberry juice (CBJ) and GFJ, respectively. The in vivo studies also showed that both CBJ and GFJ enhanced the oral bioavailability of TDF as the AUC was increased by 24% and 97%, respectively.

4. These results indicate that the prevention of the metabolic conversion of TDF to its monoester form is crucial in increasing the oral absorption of TDF.

Keywords:

• Esterases
• fruit juices
• P-glycoprotein
• pharmacokinetics
• tenofovir disoproxil fumarate

Acknowledgements

Joseph Shailender was awarded senior research fellowship (09/1026 (0015)/2014 EMR-I) from Council for Scientific and Industrial Research (CSIR) to pursue doctoral studies.

Declaration of interest

The authors declare that they have no conflict of interest.

Supplementary material available online