The amount and composition of gastrointestinal media are crucial parameters in oral drug delivery. In fasted state, variable residual gastric volumes and gastric emptying behavior often cause variable drug release and absorption from oral drug products. Unfortunately, interindividual and intraindividual variability of the gastric conditions in fasted state are currently insufficiently mapped. In this work, datasets from 5 MRI studies with 16 treatments in total were pooled. The interindividual and intraindividual variability of residual gastric volumes after 10 h overnight fasting and the subsequent emptying of 240 mL of water were compared in healthy human subjects under conditions mimicking clinical studies. This work shows that even under standardized clinical conditions, residual gastric volumes and water emptying are highly variable. Interestingly, interindividual and intraindividual variabilities of both parameters were comparable, suggesting that the variability within the studies was mainly resulting from intraindividual day-to-day variations. The mean resting volumes in all conducted investigations amounted to 25 ± 18 mL (n = 120). Furthermore, 85 ± 13% (n = 22) of initially available gastric volume (resting volume plus 240 mL) was emptied after 30 min. The findings of this work will hopefully contribute to a better comprehension of the variability of oral drug release and absorption.
Keywords: Biorelevant dissolution; Fasted stomach; Gastrointestinal volumes; Magnetic resonance imaging; PBPK; Variability.
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