Mifepristone (RU486), an 11beta-substituted nor-steroid containing a 17alpha-1-propynyl group used clinically as an antiprogestin agent for medical abortions, was demonstrated to be a selective mechanism-based inactivator of human cytochrome P-450-3A4 (CYP-3A4). The loss of testosterone 6beta-hydroxylation activity was time- and concentration-dependent as well as requiring metabolism of mifepri...

We present a relatively simple, abstract, yet mechanistically realistic, in silico intestinal device (ISID). Its design enabled exploration of the mechanistic details of absorption for passively absorbed compounds that are also dual substrates of drug-metabolizing enzymes (cyp) and transporters (pgp), including P-glycoprotein. cyp and pgp, functioning as validated analogs of their referents, ar...

Pigment Yellow 74 (PY74) is a monoazo pigment that is used in yellow tattoo inks. The metabolism of PY74 was investigated using rat liver and human liver microsomes and expressed human cytochromes P450 (P450s). Two phase I metabolites were isolated and characterized by mass spectrometry and NMR techniques. One metabolite (PY74-M1) was a ring hydroxylation product of PY74, 2-((2-methoxy-4-nitrop...

Trazpiroben (TAK-906), a peripherally selective dopamine D2/D3 receptor antagonist, is being developed for the treatment of patients with gastroparesis. The potential trazpiroben to act as perpetrator or victim cytochrome P450 (CYP)- transporter- mediated drug–drug interactions (DDIs) was evaluated following latest regulatory guidelines.In vitro studies revealed that metabolised mainly through ...

Single nucleotide polymorphism (SNP) genotype frequencies were examined to determine whether variation in 6 estrogen-related genes was associated with differences in cognitive functioning in women at midlife. DNA from a multiracial/multiethnic sample of 875 African American, Caucasian, Chinese, and Japanese women aged 45 to 56 years participating in the Study of Women's Health Across the Nation...

Objectives: Children and young people (CYP) with special educational needs (SEN) are more likely to experience disturbed sleep poor mental wellbeing. This study explored the differential impact of coronavirus disease 2019 (COVID-19) pandemic on wellbeing CYP without SEN.Methods: The National Institute Health Research Young People MedTech Cooperative, Sheffield Children’s Service (NHS) Foundatio...

The maintenance of the major hepatic cytochrome P450 (CYP) enzymes has been studied in precision-cut human liver slices cultured for up to 72 h in supplemented RPMI 1640 medium. The relative apoprotein levels of 11 CYP enzymes were determined using a panel of antipeptide antibodies. In addition, 7-ethoxyresorufin O-deethylase, tolbutamide methylhydroxylase, debrisoquine 4-hydroxylase, and testo...

In the present study, the effect of CP-001, a standardized herbal mixture of Houttuynia cordata, Rehmannia glutinosa, Betula platyphylla, and Rubus coreanus, on cytochrome P450 (CYP) enzyme-mediated drug metabolism was investigated in vitro to evaluate the potential for herb-drug interactions. CP-001 was tested at concentrations of 1, 3, 10, 30, and 100  μ g/mL. A CYP-specific substrate mixture...