The open source database “OpenCYP database” has been developed based on the results of extensive literature searches from peer-reviewed literature. OpenCYP provides data human variability baseline activities and polymophism frequencies for selected cytochrome P-450 isoforms (CYP1A2, CYP2A6, CYP2D6, CYP3A4/3A5 CYP3A7) in healthy adult populations world populations. CYP enzymatic were generally e...

The effects of modified cyclodextrins (CDs) hydroxypropyl-beta-CD and methyl-beta-CD were studied in vitro on cDNA-expressed human cytochrome P-450 (CYP) activities (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). The modified CDs inhibited the activities of CYP2C19 and CYP3A4 while enhancing CYP2C9 activity by 140 to 176% relative to the control values at lower concentrations. In addition, methy...

BACKGROUND AND OBJECTIVE Dried blood spot (DBS) sampling has gained wide interest in bioanalysis during the last decade and has already been successfully applied in pharmacokinetic and phenotyping studies. However, all of the available phenotyping studies used small datasets and did not include a systematic evaluation of DBS-specific parameters. The latter is important since several of these fa...

Rutaecarpine, evodiamine, and dehydroevodiamine are quinazolinocarboline alkaloids isolated from a traditional Chinese medicine, Evodia rutaecarpa. The in vitro effects of these alkaloids on cytochrome P450 (P450)-catalyzed oxidations were studied using mouse and human liver microsomes. Among these alkaloids, rutaecarpine showed the most potent and selective inhibitory effect on CYP1A-catalyzed...

In order to Investigate the metabolic activation pathway of food-derived heterocyclic amities, 2-amino-3-metbylimldazo[4,5-fjquinoline (IQ) and 2-amino-3,8-dlmethyllmidaw[4,5-fjquinoxallne (MeIQx), cultured cell lines which stably expressed human cytochrome P4501A2 (CYP1A2) and N-acetyltransferases (NATs) were developed by the method of comple mentary DNA (cDNA) transfection. First, a cell line...

The contribution of CYP1A2 to the metabolism of the dietary heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in vivo in humans, has been determined with furafylline, a highly selective inhibitor of this enzyme. The inhibitory potential of furafylline in vivo was first assessed by determining its effect on clear...

Coffee and caffeine consumption has been associated with ovarian cancer risk in several epidemiological studies. CYP1A2 is a key enzyme in the metabolism of coffee and in the activation of heterocyclic aromatic compounds that may be carcinogenic. Data from a preliminary investigation conducted in Hawaii of 164 epithelial ovarian cancer cases and 194 controls were used to examine the hypothesis ...

In a previous study using microsomes from human lymphoblastoid cell lines (HLCL) containing single cDNA-expressed human cytochrome P450 (P450) enzymes, human P450 enzymes were identified that are susceptible to mechanism-based inactivation by the porphyrinogenic xenobiotics, 3-[(arylthio)ethyl]sydnone (TTMS), 3,5-diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine (4-ethylDDC) and allylis...

Due to the importance of in vitro cytochrome P450 (P450) induction assay to assess the possible drug-drug interaction events, the recent US Food and Drug Administration draft guidance and European Medicines Agency guideline recommend to assess P450 induction using fresh or cryopreserved hepatocytes at mRNA level and/or enzyme activity level. Although cryopreserved hepatocytes are commercially a...

Meranzin hydrate (MH), an absorbed bioactive compound from the Traditional Chinese Medicine (TCM) Chaihu-Shugan-San (CSS), was first isolated in our laboratory and was found to possess anti-depression activity. However, the role of cytochrome P450s (CYPs) in the metabolism of MH was unclear. In this study, we screened the CYPs for the metabolism of MH in vitro by human liver microsomes (HLMs) o...