Cancer prevention
High-molecular-weight macrogol (e.g., 8000 g/mol) has been shown to be a dietary preventive agent against colorectal cancer in animal models. The Chemoprevention Database shows macrogol is the most effective known agent for the suppression of chemical carcinogenesis in rats. Cancer prevention applications in humans, however, have not yet been tested in clinical trials. Other
Macrogol is also used to fuse B-cells with myeloma cells in monoclonal antibody production. References
External links
"Macrogol". Drug Information Portal. U.S. National Library of Medicine.
Pharmacokinetics
Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of seven to eight hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the acetamide group, and secondarily through hydroxylation mediated by the liver enzyme CYP2C19. The three major metabolites (hydroxy, acid, and hydroxyacid) are pharmacologically inactive. Brivaracetam is eliminated as urinary metabolites, with over 95% of a radioactive test dose recovered in the urine within 72 hours, including only 8.6% as unchanged brivaracetam. Pharmacogenetics
As noted above, brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, "CYP2C19 poor metabolizers", will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea. The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction. Chemical and physical properties
Brivaracetam is the 4R-propyl analogue of the anticonvulsant levetiracetam.