QUANTITATIVE PREDICTION OF DRUG-DRUG INTERACTIONS: MECHANISM-BASED INHIBITION OF DRUG METABOLISM
نویسندگان
چکیده
منابع مشابه
Prediction of in vivo drug-drug interactions based on mechanism-based inhibition from in vitro data: inhibition of 5-fluorouracil metabolism by (E)-5-(2-Bromovinyl)uracil.
The fatal drug-drug interaction between sorivudine, an antiviral drug, and 5-fluorouracil (5-FU) has been shown to be caused by a mechanism-based inhibition. In this interaction, sorivudine is converted by gut flora to (E)-5-(2-bromovinyl)uracil (BVU), which is metabolically activated by dihydropyrimidine dehydrogenase (DPD), and the activated BVU irreversibly binds to DPD itself, thereby inact...
متن کاملRisk assessment of mechanism-based inactivation in drug-drug interactions.
Drug-drug interactions (DDIs) that occur via mechanism-based inactivation of cytochrome P450 are of serious concern. Although several predictive models have been published, early risk assessment of MBIs is still challenging. For reversible inhibitors, the DDI risk categorization using [I]/K(i) ([I], the inhibitor concentration; K(i), the inhibition constant) is widely used in drug discovery and...
متن کاملMechanism-based inactivation of human cytochrome p450 enzymes and the prediction of drug-drug interactions.
The ability to use vitro inactivation kinetic parameters in scaling to in vivo drug-drug interactions (DDIs) for mechanism-based inactivators of human cytochrome P450 (P450) enzymes was examined using eight human P450-selective marker activities in pooled human liver microsomes. These data were combined with other parameters (systemic C(max), estimated hepatic inlet C(max), fraction unbound, in...
متن کاملEffects of CYP2C9*3 and CYP2C9*13 on Diclofenac Metabolism and Inhibition-based Drug-Drug Interactions.
Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9*13 are the principal variant alleles found in the Chinese population. CYP2C9*3 has been reported to reduce the metabolism of diclofenac and alter the extent of drug-drug interactions (DDIs). The effects of CYP2C9*13 on diclofenac metabolism are n...
متن کاملQuantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?
This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug-drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Drug Metabolism and Pharmacokinetics
سال: 1998
ISSN: 0916-1139
DOI: 10.2133/dmpk.13.supplement_94