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• W2091089634 abstract "The selective EGFR tyrosine kinase inhibitor, gefitinib has been shown to be active against certain human carcinomas. It had been noted that a proportion of volunteers consistently had lower gefitinib exposure following oral administration. The shape of the elimination profile in this subset was also different, showing a monophasic elimination pattern rather than the biphasic pattern observed in the majority of subjects. A gamma scintigraphic study was conducted to examine the relationship of gastrointestinal transit and drug absorption in a cohort of rapid clearance subjects (n = 5) and normal profile volunteers (n = 7). The fasted volunteer panel received a 250 mg gefitinib tablet labelled with [111In]–DTPA together with 240 mL [99mTc]-labelled water. The rapid clearance cohorts were shown to have a faster mean gastric emptying T90 (37 min vs 74 min) and shorter small intestinal transit time (156 min vs 204 min), resulting in an earlier colonic arrival time (181 min vs 244 min). Mean plasma Cmax was lower (99.2 ng/mL vs 116 ng/mL) and AUC almost half in the rapid clearance group (2162 ± 81 ngh/mL vs 4996 ± 64 ngh/mL). These data suggest that gastrointestinal transit parameters play a role in the differences in the rapid clearance profile group, also contributing to the biphasic to monophasic switch. However, historical data show, at the recommended dose of 250 mg/day steady-state plasma concentrations adequate for clinical benefit are achieved in patients with non-small cell lung cancer." @default.
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• W2091089634 date "2009-07-01" @default.
• W2091089634 modified "2023-10-17" @default.
• W2091089634 title "Do gastrointestinal transit parameters influence the pharmacokinetics of gefitinib?" @default.
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• W2091089634 doi "https://doi.org/10.1016/j.ijpharm.2009.04.008" @default.
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