2.5. Pharmacokinetic Properties

The "D" and "E" in ADMET stand for distribution and elimination (or excretion). Both are functions of the degree to which a drug is bound up in the circulation or in tissues. ADMET Predictor addresses these potential development issues by providing models for the fraction unbound in human, rat, mouse, dog, and monkey plasma (fup_hum, fup_rat, fup_mou, fup_dog and fup_mky); blood to plasma ratios in human, rat, mouse, dog, and monkey (RBP_hum, RBP_rat, RBP_mou, RBP_dog, and RBP_mky); and fraction unbound in microsomes (fumic_hum, fumic_rat, fumic_mou, fumic_dog, and fumic_mky) as well as hepatocytes (S+fuhep); and volume of distribution at the steady state (Vd).

Clearance classification is addressed by our implementation of the Extended Clearance Classification System (ECCS) proposed by Varma et al. (2015), which is based on predicted physicochemical properties. Assigning suitable thresholds for ionization, permeability and molecular weight defines six property classes, each of which they identified with drugs whose clearance is controlled predominantly by metabolism, renal excretion or hepatic uptake.We also provide a complementary model ([S+CL_Mech]) based on molecular descriptors that gives the dominant clearance pathway directly. Three binary ANNE models ([S+CL_Metab], [S+CL_Renal] and [S+CL_Uptake]) are provided that predict whether the corresponding pathway is likely to be important or not for a given compound.

ADMET Predictor also offers an interactive graphical window to explore how compounds are classified under BCS and DCS. The Biopharmaceutics Classification System is based on drug solubility and permeability (Amidon 1995). It is widely used by the pharmaceutical industry in the evaluation of drug candidates and by the U.S. FDA in deciding whether or not to grant for bioavailability and bioequivalence study waivers. The Developability Classification System was subsequently designed to assess the likelihood of success in oral drug development (Butler 2010).