RepTTTARS.MIX {bear} | R Documentation |
The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inflection point of the curve (Cinpt at Tinpt). The inflection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best fit. It starts with the last three data points from the concentration-time profile, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax).
With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed.
Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identification of the Mono-Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008).