↵ a Blood samples were collected from three individual animals per time point. Plasma concentrations of GV196771 and GF120918 were determined by LC-MS/MS analysis. Group means and standard deviations of plasma concentrations were calculated at each sampling time point and pharmacokinetic parameters were determined by destructive noncompartmental analysis of the mean plasma concentrations

↵ b The GF120918 plasma concentrations ranged from 2340 to 815 ng/ml during the 0- to 6-h time period after dosing GV196771. The mean (± standard deviation) GF120918 concentrations over this 6-h time period used for GV196771 blood sampling were 1309 ± 475 ng/ml in wild-type animals and 1602 ± 485 ng/ml in Pgp-deficient animals (P > 0.05). The GF120918 AUC_{(0→24 h)} values were 7775 and 8707 ng · h/ml in the wild-type and Pgp-deficient animals, demonstrating that there was no difference (P > 0.05) in the plasma concentrations of GF120918 between theses groups

↵ c The fold change values are calculated by comparison with wild-type mice

↵ d P < 0.001 compared with the area under the curve (AUC) for wild-type mice. AUC and associated variance was determined by the method of Bailer (1988) for pharmacokinetic studies involving destructive sampling. Statistical significance was determined using Student's t test or, in the case of AUC, by using the z-statistic for the normal distribution table (Bailer, 1988)

↵ e Even though the fold change was notable (1.60-fold), the results were not statistically significant (P > 0.05) for comparisons of the AUC for wild-type mice treated with GF120918 and mdr1a/1b^-/- (P = 0.097) or mdr1a/1b^-/- mice pretreated with GF120918 (P = 0.099)

↵ f P < 0.005 for comparison of the AUC for mdr1a/1b^-/- and mdr1a/1b^-/- mice pretreated with GF120918