Holt, Kimberly published the artcilePrediction of tissue-plasma partition coefficients using microsomal partitioning: incorporation into physiologically based pharmacokinetic models and steady-state volume of distribution predictions, Formula: C18H19Cl2NO4, the main research area is plasma partition coefficient protein binding microsomal partitioning PBPK model.
Drug distribution is a necessary component of models to predict human pharmacokinetics. A new membrane-based tissue-plasma partition coefficient (Kp) method (Kp,mem) to predict unbound tissue to plasma partition coefficients (Kpu) was developed using in vitro membrane partitioning [fraction unbound in microsomes (fum)], plasma protein binding, and log P. The resulting Kp values were used in a physiol. based pharmacokinetic (PBPK) model to predict the steady-state volume of distribution (Vss) and concentration-time (C-t) profiles for 19 drugs. These results were compared with Kp predictions using a standard method [the differential phospholipid Kp prediction method (Kp,dPL)], which differentiates between acidic and neutral phospholipids. The Kp,mem method was parameterized using published rat Kpu data and tissue lipid composition The Kpu values were well predicted with R2 = 0.8. With one outlier removed for Kp,mem and two for Kp,dPL, the Vss predictions for R2 were 0.80 and 0.79 for the Kp,mem and Kp,dPL methods, resp. The C-t profiles were also predicted and compared. Overall, the Kp,mem method predicted the Vss and C-t profiles equally or better than the Kp,dPL method. An advantage of using fum to parameterize membrane partitioning is that fum data are used for clearance prediction and are, therefore, generated early in the discovery/development process. Also, the method provides a mechanistically sound basis for membrane partitioning and permeability for further improving PBPK models.
Drug Metabolism & Disposition published new progress about Adipose tissue. 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, Formula: C18H19Cl2NO4.