Relative plasma, brain and cerebrospinal fluid (CSF) exposures and unbound fractions in
plasma and brain were examined for 18 proprietary compounds in rats. The relationship …

Quantitative prediction of human pharmacokinetics is critical in assessing the viability of drug
candidates and in determining first‐in‐human dosing. Numerous prediction methodologies…

Cytochrome P450 constitute a superfamily of heme-containing enzymes that catalyze the
oxidative biotransformation of structurally diverse xenobiotics including drugs. Inhibition of …

The P-glycoprotein (P-gp)-deficient mouse model is used to assess the influence of P-gp-mediated
efflux on the central nervous system (CNS) distribution of drugs. The steady-state …

Volume of distribution is one of the most important pharmacokinetic properties of a drug
candidate. It is a major determinant of half-life and dosing frequency of a drug. For a similar log P…

Unbound fractions in mouse brain and plasma were determined for 31 structurally diverse
central nervous system (CNS) drugs and two active metabolites. Three comparisons were …

Although approaches to the prediction of drug-drug interactions (DDIs) arising via time-dependent
inactivation have recently been developed, such approaches do not account for …

Drug half-life has important implications for dosing regimen and peak-to-trough ratio at the
steady state. A half-life of 12–48 h is generally ideal for once daily dosing of oral drugs. If the …

Compound 4 (PF-04971729) belongs to a new class of potent and selective sodium-dependent
glucose cotransporter 2 inhibitors incorporating a unique dioxa-bicyclo[3.2.1]octane (…

Due to its implications for both dose level and frequency, clearance rate is one of the most
important pharmacokinetic parameters to consider in the design of drug candidates. …