Iwasaki, Shinji published the artcileApplication of unbound liver-to-plasma concentration ratio to quantitative projection of cytochrome P450-mediated drug-drug interactions using physiologically based pharmacokinetic modelling approach, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is liver plasma cytochrome drug interaction PBPK modeling approach; Drug–drug interaction; K; human cryopreserved hepatocytes; physiologically based pharmacokinetic model.
1. This study evaluated the prediction accuracy of cytochrome P 450 (CYP)-mediated drug-drug interaction (DDI) using minimal physiol.-based pharmacokinetic (PBPK) modeling incorporating the hepatic accumulation factor of an inhibitor (i.e. unbound liver/unbound plasma concentration ratio [Kp,uu,liver]) based on 22 clin. DDI studies.2. Kp,uu,liver values were estimated using three methods: (1) ratio of cell-to-medium ratio in human cryopreserved hepatocytes (C/Mu) at 37°C to that on ice (Kp,uu,C/M), (2) multiplication of total liver/unbound plasma concentration ratio (Kp,u,liver) estimated from C/Mu at 37°C with unbound fraction in human liver homogenate (Kp,uu,cell) and (3) observed Kp,uu,liver in rats after i.v. infusion (Kp,uu,rat).3. PBPK model using each Kp,uu,liver projected the area under the curve (AUC) increase of substrates more accurately than the model assuming a Kp,uu,liver of 1 for the average fold error and root mean square error did. Particularly, the model with a Kp,uu,liver of 1 underestimated the AUC increase of triazolam following co-administration with CYP3A4 inhibitor itraconazole by five-fold, whereas the AUC increase projected using the model incorporating the Kp,uu,C/M, Kp,uu,cell, or Kp,uu,rat of itraconazole and hydroxyitraconazole was within approx. two-fold of the actual value.4.
Xenobiotica published new progress about Blood plasma. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.