Bevirimat - Metabolism

Metabolism

It has been found that bevirimat does not inhibit the cytochrome P450 system or interact with the human P-glycoprotein. Unformulated bevirimat is not well absorbed from the gastrointestinal tract into the blood. Some of the less desirable properties of unformulated bevirimat and its salts include: inadequate bioavailability, poor solubility of the pharmaceutical composition in gastric fluid, insufficient dispersion of bevirimat in gastric fluid, below standard long term safety profile for oral dosage forms, below standard long term chemical and physical stability of the final dosage form, tendency for conversion to metastable forms, lengthy dissolution times for oral dosage forms, and precipitation in gastric or intestinal fluids. Some pharmaceutical compositions of formulated bevirimat have shown to have better properties over unformulated bevirimat. Some of these properties include: improved bioavailability, improved solubility of the composition in gastric fluid, improved dispersion of bevirimat in gastric fluid, improved safety for oral dosage forms, improved chemical and physical stability of the oral dosage form, decreased conversion to metastable forms, and decreased rate of precipitation in gastric fluid. Bevirimat was rapidly absorbed after oral administration, with detectable concentrations present in the plasma within 15 minutes after administration and peak plasma concentrations were achieved approximately one to three hours after administration. The plasma had a mean plasma elimination half-life ranging from 58 to 80 hours. This long half-life of bevirimat supports once-daily dosing. Elimination of bevirimat is primarily via hepatobiliary routes, with renal elimination counting for less than 1% of the dose.