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Geometric mean BIBW 2992 plasma concentration¨Ctime profiles after single andmultiple dosing are shown in Figure 1. No deviation from dose-proportional behavior was observed over the evaluated dose range. Across doses, the terminal half-life of BIBW2992 ranged between 21.3 to 27.7 hours on day 1 and 22.3 to 67.0 hours on day 27. Steady-state was reached after 7 days of initiating continuous BIBW 2992 dosing, with no evidence of further drug accumulation or decrease through subsequent cycles. The poor association between apparent total body clearance and both weight and body-surface area justified the fixed oral dosing of BIBW 2992 (Appendix Fig A2, online only). Table 3 summarizes the PK parameters of BIBW 2992 on days 1 and 27 (steady-state) after single and multiple doses, and Appendix Table A2 (online only) presents the PK param- eters of drug under fed and fasted conditions. High-fat food intake before single oral BIBW 2992 doses of 40 mg/d significantly altered and decreased drug disposition. |
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sltmac(½ð±Ò+1): 2011-11-16 11:06:56
23010402(½ð±Ò+5, ·ÒëEPI+1): лл~ 2011-11-16 17:27:59
sltmac(½ð±Ò+1): 2011-11-16 11:06:56
23010402(½ð±Ò+5, ·ÒëEPI+1): лл~ 2011-11-16 17:27:59
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