BACKGROUND AND OBJECTIVE Prediction of drug clearance in liver cirrhosis patients is currently based on in vitro-in vivo extrapolation and physiologically-based pharmacokinetic models. No static model for this purpose has been described. The objectives of this study were …

Previous reports have suggested that imatinib may increase cyclosporine exposure by CYP3A4 inhibition. However, the magnitude of this drug interaction remains unclear. At present, quantitative information about the interaction profile of imatinib is scarce. METHODS The authors report …

An approach was proposed in 2007 for quantitative predictions of cytochrome P450 (CYP)3A4-mediated drug-drug interactions. It is based on two characteristic parameters: the contribution ratio (CR; i.e., the fraction of victim drug clearance by CYP) and the inhibition …

Currently, quantitative prediction of the impact of genetic polymorphism and drug-drug interactions mediated by cytochromes, based on in vivo data, is made by two separate methods and restricted to a single cytochrome. We propose a unified approach for …

We present a unified quantitative approach to predict the in vivo alteration in drug exposure caused by either cytochrome P450 (CYP) gene polymorphisms or CYP-mediated drug-drug interactions (DDI). An application to drugs metabolized by CYP2C19 is presented. The …

BACKGROUND AND OBJECTIVE Cytochrome P450 (CYP) 2C9 is the most common CYP2C enzyme and makes up approximately onethird of total CYP protein content in the liver. It metabolises more than 100 drugs. The exposure of drugs mainly eliminated …

We propose a framework to enable quantitative prediction of the impact of CYP2D6 polymorphisms on drug exposure. It relies mostly on in vivo data and uses two characteristic parameters: one for the drug and the other for the …

BACKGROUND AND OBJECTIVES An approach was recently proposed for quantitative predictions of cytochrome P450 (CYP) 3A4-mediated drug-drug interactions. This approach relies solely on in vivo data. It is based on two characteristic parameters: the contribution ratio (CR; i.e. …

Induction of cytochrome P450 (CYP) 3A4 potentially reduces the blood concentrations of substrate drugs to less than one-tenth, which results in ineffective pharmacotherapy. Although the prediction of drug-drug interactions (DDIs) that are mediated by induction of CYP3A4 has …

Cytochrome P450 (CYP) 3A4 is the most prevalent metabolising enzyme in the human liver and is also a target for various drug interactions of significant clinical concern. Even though there are numerous reports regarding drug interactions involving CYP3A4, …