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Velaparib a parp inhibitor
I did some research on Velaparib. This is a Parp inhibitor also known as ABT888. Information is sketchy as most of the trials mentioned were concerned with signing up for them but there were some results, dosages and side effects listed.
Parp is important for DNA repair and Parp inhibitors may potentiate the effect of chemo drugs like Carboplatin and Paclitaxel (Taxol). These drugs damage cancer cell DNA and the cancer cells are dependent on the Parp enzyme to repair the chemo induced damage. Radiation therapy also damages DNA and Parp inhibitors like Velaparib might also potentiate radiation thrapy
There was trial where Velaparib was combined with Whole Brain radiation to treat the brain mets of various kinds of cancers like breast, lung and melanoma. A Velaparib dosage of 200mg twice daily was well tolerated. Since Velaparib was the only drug used in this study, you get a feel for the side effects of the drug when used alone. Fatigue was common, as was headache and decreased appetite and low blood sodium (hyponatremia) and Anemia and Thrombocytopenia and some Hair loss. Also Nausea. As a whole, Velaparib was well tolerated.
It is eliminated mostly by the kidneys (70%) so it shouldnt interact too much with other medications that are metabolized by the liver. This was a human study (the 200mg Velaparib twice a day). In one rat study Velaparib crossed the blood brain barrier well. I think the concentration of Velaparib in the brain was three times the plasma level. This should hold true for humans also.
There was another study that combined Velaparib withCarbolatin AUC 6 plus Paclitaxel (Taxol) 200mg/meter squared. The Velaparib was given in a dosage of 120mg twice daily. Since Velaparib will probably be used to enhance the effects of various chemo drugs 120mg Velaparib twice daily may be a common dose. Parp stands for Poly-Adenosine Ribose Polymerase and this enzyme is used by cells for single strand ad double strand DNA repair. Parp inhibitors prevent cancer cells from repairing the damaged DNA. This post is only fragmentary as far as information goes. Im sure there will be a lot more information in the future.
Paul
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