240 mL Water Drink Study

Solid oral delivery is the most frequently used route of administration for pharmaceutical drug products. Along with other important physiological parameters, the volume of liquid in the small intestine (SILV) has the potential to greatly influence the rate and extent of drug dissolution and absorption in the GI tract, or "oral bioperformance". Modeled small bowel absorption of a drug can vary by more than five-fold as SILV decreases from 500 to 50 ml. To obtain reasonable predictions of oral bioperformance scientists must design meaningful in vitro dissolution tests and mechanistic drug transport models that capture the range of SILV in humans. However, little is known about liquid volumes in the gut, mostly due to invasiveness of previous techniques. A recent study has drawn great attention to the possibility of the liquid in the small intestine existing in discrete liquid "pockets" hence it would also be desirable to monitor the time courses and volumes of individual water pockets in the small intestine.

Magnetic resonance imaging (MRI) is the ideal tool to carry out serial and non-invasive imaging of gastrointestinal function. MRI is inherently suited to image liquid materials and this ability has been exploited to image liquids in the undisturbed gastrointestinal tract. Gastric emptying measurements have been long established and validated. Small bowel liquid volumes measurements have been recently validated against naso-duodenal infusion. Ultimately, the findings with this study will provide novel insights on the volume and distribution of ingested liquids in the gastrointestinal tract.

Inclusion criteria

• Apparently healthy; no medical conditions that might affect the study measurements
• Male or female
• Age between 18 and 55 years of age
• Body mass index (BMI) between 18.5 and 24.9 kg m-2
• Suitable for MRI scanning (eg absence of metal implants, infusion pumps and pacemakers as assessed by the MRI safety questionnaire

Exclusion criteria

• Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy)
• Known gastrointestinal disease
• Smoking
• History of alcohol or drug abuse
• Taking medication that is likely to affect gastrointestinal function
• Participation in night shift work the week prior to the study day. (Night work is defined as working between midnight and 6 am)
• Strenuous exercise greater than 10 hours per week
• Consumption of more than 21 units of alcohol in a typical week