Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control
نویسندگان
چکیده
Vertex Pharmaceuticals, Boston, Massachusetts (NH); Genentech, South San Francisco, California (JRK); Novartis Pharmaceuticals, Florham Park, New Jersey (HE); Eli Lilly and Company, Indianapolis, Indiana (MM); Boehringer Ingelheim, Ridgefield, Connecticut (DR); Merck and Co., Kenilworth, New Jersey (JP), Amgen Inc., Thousand Oaks, California (JD), Pfizer Global Research and Development, Groton, Connecticut (OAF); Sanofi Pharmaceuticals, ChillyMazarin, France (MP); Eisai Pharmaceuticals, Andover, Massachusetts (AYS); Glaxo SmithKline, King of Prussia, Pennsylvania (LC); Bristol Myers Squibb, Wallingford, Connecticut (MS); AstraZeneca, Mölndal, Sweden (BJ); EMD Serono, Billerica, Massachusetts (RW); Janssen R&D, Spring House, Pennsylvania (SD); Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Co., Cambridge, Massachusetts (SKB); Corning Life Sciences; Woburn, Massachusetts (GZ); XenoTech LLC, Lenexa, Kansas (DB), Merck and Co., West Point, Pennsylvania (DT) This article has not been copyedited and formatted. The final version may differ from this version. DMD Fast Forward. Published on June 23, 2017 as DOI: 10.1124/dmd.116.074567
منابع مشابه
Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Focus on Downregulation, CYP2C Induction, and CYP2B6 Positive Control.
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency (PMDA), and the Food and Drug Administration (FDA) have issued guidelines for the conduct of drug-drug interaction studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovati...
متن کاملCalcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes.
The expression of three cytochromes P450 (CYP3A4, CYP2C9, and CYP2B6) was investigated in primary human hepatocyte cultures following treatment with four calcium channel modulators (CCM) of the dihydropyridine family, three antagonists (nifedipine, nicardipine, and isradipine), and one agonist (BK8644). Induction of CYP3A4 was studied by Northern blot, Western blot, and enzymatic activity. Indu...
متن کاملInduction of CYP2C genes in human hepatocytes in primary culture.
The expression and inducibility of four CYP2C genes, including CYP2C8, -2C9, -2C18, and -2C19, was investigated in primary cultures of human hepatocytes. By the use of RNase protection assay and specific antibodies, each CYP2C mRNA and protein were quantified unequivocally. The four CYP2C mRNAs were expressed in human livers and cultured primary hepatocytes, but only the CYP2C18 protein was not...
متن کاملCytochrome P450 3A4 mRNA is a more reliable marker than CYP3A4 activity for detecting pregnane X receptor-activated induction of drug-metabolizing enzymes.
Induction of cytochrome P450 (P450) activity in the clinic can result in therapeutic failure such as tissue rejection in transplant patients or unwanted pregnancy, among others. CYP3A4 is by far the most abundant isoform and is responsible for the majority of P450-related metabolism of all marketed drugs. However, it is of importance to understand the significance of induction mediated through ...
متن کاملP-207: Pharmacogenetic Study of CYP19A1 (Aromatase) in Ovarian Induction in Iranian Polycystic Ovarian Syndrome Patients
Background: Hyper-androgenemia is one of the main clinical features of polycystic ovarian syndrome (PCOS). Letrozol is an aromatase inhibitor drug, which is co-administered with gonadotropins in most cases of PCOS, to improve ovulation. Aromatase has a critical role in catalyzing the conversion of androgens to estrogens and is responsible for keeping the homeostatic balance between them. Hence ...
متن کامل