. . . . "Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved on July 20, 2012. "@en . . . "Following intravenous administration of doses \u2265 15 mg/m^2, carfilzomib was rapidly cleared from the systemic circulation with a half-life of \u2264 1 hour on Day 1 of Cycle 1."@en . . "Kyprolis"@en . . "868540-17-4"@en . . . "Over the concentration range of 0.4 - 4 micromolar, carfilzomib was 97% protein bound. "@en . . "Vd, steady state, 20 mg/m^2 = 28 L "@en . "Cmax, single IV dose of 27 mg/m^2 = 4232 ng/mL; AUC, single IV dose of 27 mg/m^2 = 379 ng\u2022hr/mL; Carfilzomib does not accumulation in the systemic. At doses between 20 and 36 mg/m2, there was a dose-dependent increase in exposure."@en . . . . . . . . . . "Humans and other mammals"@en . "PR-171"@en . . . . . . . . . . "Systemic clearance = 151 - 263 L/hour. As this value exceeds hepatic blood flow, it suggests that carfilozmib is cleared extrahepatically. "@en . "# Kortuem KM, Stewart AK: Carfilzomib. Blood. 2013 Feb 7;121(6):893-7. doi: 10.1182/blood-2012-10-459883. \"Pubmed\":http://www.ncbi.nlm.nih.gov/pubmed/23393020 # Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ: Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007 Nov 1;110(9):3281-90. Epub 2007 Jun 25. \"Pubmed\":http://www.ncbi.nlm.nih.gov/pubmed/17591945"@en . . . . . . . . . . "Most commonly reported adverse reactions (incidence \u2265 30%) are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. The two dose limiting toxicities are thrombocytopenia and febrile neutropenia. Maximum tolerate dose = 15 mg/m^2 "@en . . "Carfilzomib"@en . . . . " "@en . "Carfilzomib is indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. "@en . . . "Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (\u03B25 and \u03B25i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites. "@en . . "approved"@en . . . . .