Fujioka, Yasushi published the artcileRisk assessment of mechanism-based inactivation in drug-drug interactions, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is risk assessment drug interaction CYP inhibitor model; cytochrome P450 inhibitor drug interaction risk assessment model.
Drug-drug interactions (DDIs) that occur via mechanism-based inactivation of cytochrome P 450 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]/Ki ([I], the inhibitor concentration; Ki, the inhibition constant) is widely used in drug discovery and development. Although a simple and reliable methodol. such as [I]/Ki categorization for reversible inhibitors would be useful for mechanism-based inhibitors (MBIs), comprehensive anal. of an analogous measure reflecting in vitro potency for inactivation has not been reported. The aim of this study was to evaluate whether the term λ/kdeg (λ, 1st-order inactivation rate at a given MBI concentration; kdeg, enzyme degradation rate constant) would be useful in the prediction of the in vivo DDI risk of MBIs. Twenty-one MBIs with both in vivo area under the curve (AUC) change of marker substrates and in vitro inactivation parameters were identified in the literature and analyzed. The results of this anal. show that in vivo DDIs with >2-fold change of object drug AUC can be identified with the cutoff value of λ/kdeg = 1, where unbound steady-state Cmax is used for inhibitor concentration However, the use of total Cmax led to great overprediction of DDI risk. The risk assessment using λ/kdeg coupled with unbound Cmax can be useful for the DDI risk evaluation of MBIs in drug discovery and development.
Drug Metabolism & Disposition published new progress about Drug interactions. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem