Student's t-test and SYSTAT12 software (Systat Software Inc., Chicago, IL, USA) were used to analyze differences in mean BPA and BPAG pharmacokinetic parameters ([AUC.sub.last], [C.sub.max] , [T.sub.max], and MRT) by route of administration.
The values for pharmacokinetic parameters of BPA and BPAG obtained for different doses via different routes (iv, sublingual, and orogastric) of BPA administration are presented in Tables 1 and 2.
For BPAG, the mean [C.sub.max] did not significantly differ by route of administration (15,657 [+ or -] 6,426 vs.
The mean BPA [AUC.sub.last] (normalized to administered dose) in response to sublingual administration of BPA at 5 mg/kg was lower than that obtained after iv administration (p = 0.04; Table 1, Figure 2A), whereas the corresponding mean BPAG [AUC.sub.last] values were not significantly different.
BPA was not detected by about 2 hr after iv or sub lingual BPA administration (0.05 mg/kg), whereas BPAG plasma levels in three dogs remained > LOQ for 8-10 hr after BPA administration.
For BPAG, the mean [C.sub.max] after sublingual dosing was lower than that after iv administration (78 [+ or -] 38 for iv vs.
The mean BPA sublingual bioavailability for the 0.05 mg/kg dose was 90 [+ or -] 26%, as computed by the mean ratio of the BPAG [AUC.sub.last] values obtained for the sublingual route to the equivalent BPAG [AUC.sub.last] for the iv route.
This value was lower than the mean ratio of BPAG AUC values (54 [+ or -] 19%), showing that BPA was rather well absorbed by the gastrointestinal tract but that most absorbed BPA is metabolized by a first-pass effect at the hepatic level.
This finding was supported by the high extent of BPA bioavailability computed using systemic exposure to BPAG (81%).
In addition when considering BPAG, the bioavailability of BPA after administration of a low BPA dose (0.05 mg/kg) can be properly computed and was 90%.
Another major finding of the present study is that the two pathways of BPA systemic availability (i.e., with or without a hepatic first-pass effect) can be easily distinguished by taking into account the plasma BPAG:BPA molar concentration ratio.
Our study further shows that the BPAG:BPA plasma concentration ratio clearly differentiates the routes of BPA entry into to the systemic circulation with or without bypassing the liver.