Reference of 91-00-9, As an important bridge between the micro and macro material world, chemistry is one of the main methods and means for humans to understand and transform the material world. 91-00-9, Name is Diphenylmethanamine, SMILES is NC(C1=CC=CC=C1)C2=CC=CC=C2, belongs to amides-buliding-blocks compound. In a article, author is Elsayed, Mohamed S. A., introduce new discover of the category.
Human mass balance study and metabolite profiling of C-14-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer
Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive, ovarian, fallopian tube, or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Significant improvements in PFS were seen in all patient cohorts regardless of biomarker status. This study evaluates the absorption, metabolism and excretion (AME) of C-14-niraparib, administered to six patients as a single oral dose of 300 mg with a radioactivity of 100 mu Ci. Total radioactivity (TRA) in whole blood, plasma, urine and faeces was measured using liquid scintillation counting (LSC) to obtain the mass balance of niraparib. Moreover, metabolite profiling was performed on selected plasma, urine and faeces samples using liquid chromatography – tandem mass spectrometry (LC-MS/MS) coupled to off-line LSC. Mean TRA recovered over 504 h was 47.5% in urine and 38.8% in faeces, indicating that both renal and hepatic pathways are comparably involved in excretion of niraparib and its metabolites. The elimination of C-14-radioactivity was slow, with t(1/2) in plasma on average 92.5 h. Oral absorption of C-14-niraparib was rapid, with niraparib concentrations peaking at 2.49 h, and reaching a mean maximum concentration of 540 ng/mL. Two major metabolites were found: the known metabolite M1 (amide hydrolysed niraparib) and the glucuronide of M1. Based on this study it was shown that niraparib undergoes hydrolytic, and conjugative metabolic conversions, with the oxidative pathway being minimal.
Reference of 91-00-9, Each elementary reaction can be described in terms of its molecularity, the number of molecules that collide in that step. The slowest step in a reaction mechanism is the rate-determining step.you can also check out more blogs about 91-00-9.