Lexaria Bioscience has released preclinical data on technology intended to enhance oral delivery of antiviral drugs. The data cover the use of application of DehydraTECH to HIV drugs, but Lexaria is also exploring its use in the enhancement of antivirals against the pandemic coronavirus.
DehydraTECH is designed to improve the bioavailability of lipophilic compounds. The process entails combining a compound with fatty acids through a dehydration synthesis reaction. In doing so, Lexaria thinks it can increase intestinal absorption and cut metabolism by the liver, thereby enabling more of the drug to reach its target when given orally.
The idea is underpinned by evidence of the preferential absorption of fatty acids in the gut. Lexaria has previously claimed the technology can increase intestinal absorption by up to 10 times and cut onset of action to as few as 15 minutes.
To assess the applicability of DehydraTECH to antiviral drugs, Lexaria formulated protease inhibitor darunavir and non-nucleoside reverse transcriptase inhibitor efavirenz using its technology. Darunavir and efavirenz are HIV drugs sold in branded forms as, respectively, Prezista and Sustiva by Johnson & Johnson and Bristol Myers Squibb. Darunavir is extensively metabolized by the liver and sufferers from low bioavailability when given as a single agent.
Lexaria administered enhanced and standard versions of the antivirals to 40 rats, with 10 rats per arm of the study, and monitored the amount of drug in the animals’ blood for 24 hours.
The AUClast, defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration, for the DehydraTECH-enhanced darunavir was 721 hr∙ng/mL. The control figure was 469 hr∙ng/mL. Lexaria put the p-value for the darunavir study at 0.036.
Applied to efavirenz, DehydraTECH achieved an AUClast of 752 hr∙ng/mL, compared to 650 hr∙ng/mL in the control group. The p-value for that comparison was 0.11. The rats behaved normally with no adverse effects in either DehydraTECH cohort, according to Lexaria.
Lexaria plans to use the study as a launchpad for more work on antivirals. Starting in January, the company will study the application of DehydraTECH to antiviral drugs used in the treatment of HIV and COVID-19.
Gilead’s nucleotide variant remdesivir, the most widely used antiviral against COVID-19 to date, is given via intravenous infusion over 30 to 120 minutes. The choice is underpinned by preclinical tests that showed first-pass metabolism causes low bioavailability of remdesivir when given orally. As a prodrug, remdesivir is converted in the gut into a different form, preventing absorption. Gilead is testing an inhaled formulation.