Table 1.

Definition of Pharmacokinetic Parameters

Pharmacokinetic Parameter	Definition
tmax	Time of observed maximum concentration
Cmax	Observed maximum concentration
Ctrough	Concentration just prior to dosing measured once weekly in multiple dose studies
AUC	Area under the curve, from dosing to infinity. Calculated by the linear trapezoidal rule time 0 hour extrapolated to infinity
AUC0–24h	Area under the concentration–time curve from 0 to 24 hours post-dose, calculated on Days 1 and 4 for multiple dose studies
AUC0–96h	Area under the concentration–time curve from 0 to 96 hours post-dose
AUClast	Area under the concentration–time curve calculated by the linear trapezoidal rule time 0 hour to last time “t” hours after dosing, where t is the time point of last observable drug concentration
t1/2	Terminal half life estimated as 0.693/λz, λz is the terminal rate constant determined by log-linear regression on the terminal log-linear part of the concentration–time curve
Vz/F	Volume of distribution after extravascular administration, based on terminal phase Vz/F = Dose/(AUC × λz)
CL/F	Apparent total plasma clearance of drug after extravascular administration CL/F = Dose/AUC
RAC	Ratio of accumulation defined as AUC0–24h from multiple dose data/AUC0–24h from single dose data