The objectives of this study were to compare the drug-metabolizing activity of human CYP2D6.24 (I297L), CYP2D6.26 (I369T), CYP2D6.27 (E410K) allelic isoforms with wild-type CYP2D6.1, and to express the CYP2D7 protein derived from an indel polymorphism (CYP2D7 138delT) and investigate its possible codeine O-demethylase activity. Successful creation of individual cDNAs corresponding to CYP2D6*24 ...

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 ...

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...

Lymphoedema in children and young people (CYP) can cause significant impact affecting physical, psychological social wellbeing. This audit of 286 CYP with (2015–2018) is the first national cohort reported provides new information on patient outcome (PROM) changes over time. Conservative therapy produced statistically change measures relating to swelling, infection, appearance compression garmen...