Winnonlin professional edition version 2

Pharmacokinetic analyses of fluvastatin plasma samples followed the techniques first described for our atorvastatin-rifampin interaction study^{4 (link)} using both noncompartmental analyses and two-compartmental modeling with first order absorption using WinNonlin Professional Edition Version 2.1 (Pharsight, Mountain View, CA, USA). Non-compartmental analysis yielded parameters including area under the concentration versus time curve from time zero to the last time point (AUC_0-last), area under the curve from time zero to infinity (AUC_0−∞), area under the moment time curve from time zero to infinity (AUMC_0−∞), maximal concentration (C_max), time to maximal concentration (T_max), terminal half-life (t_1/2,z), and apparent clearance (CL/F). Two-compartmental analysis yielded the first order absorption rate constant (k_a), the reciprocal of which is the mean absorption time (MAT). MRT was calculated as the ratio of the AUMC to AUC minus MAT (i.e., $MRT=\frac{A{UMC}_{0-\infty }}{{AUC}_{0-\infty }}-MAT).$ Apparent volume of distribution at steady state (V_ss/F) was calculated^{20 (link)} as $\frac{V_{ss}}{F}=\frac{CL}{F}·MRT.$