Gastric function measurements in drug development

Abstract

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.

The effects of gastric digestion on codfish allergenicity

“…31 Furthermore, acidity per se has an important influence on digestion by acidic hydrolysis. 32 Thus the physiologic digestive function of the stomach depends to a great extent on the gastric acid secretion. In consequence, conditions with low net acid output, like, for example hypoacidity as a physiologic feature in newborns, atrophic gastritis, or partial gastrectomy, might critically affect the digestive , and 1-hour digested , cod extract) indicate the relative percentage of released histamine calculated from the total histamine content of lysed cells, which was set at 100%.…”

The gut in the beaker: Missing the surfactants?

“…After a meal, the matrix distributed in the stomach is non-uniform, with channels of liquid travelling around consolidating food masses, which are stacked from the greater curvature and as food is digested, small particles empty with the liquid phase. It has been generally accepted that preparations that dissolve or form particles of less than 2 mm in diameter pass through the stomach in a similar fashion to liquids and are less likely to be influenced by gastroparesis (Pohle & Domschke 2003). Particles can empty as boluses, mix in with the food, or partially stratify according to when during the meal the formulations are consumed (O'Reilly et al, 1987).…”

Chloroplast-Derived Therapeutic and Prophylactic Vaccines

“…US Pharmacopeia cited gastric conditions include a 3.2 mg/ml concentration of Pepsin within a simulated gastric fl uid ( 0.2% (w/v) NaCl in 0.7% (v/v) HCl (Herman et al 2005(Herman et al , 2006 . As the duration of stomach-based digestion is dependant on particle size, disparate stomach contents could prolong the exposure of target antigen to the conditions of the stomach; a time lapse of digestion is important to demonstrate stability for longer periods of time (Pohle and Domschke 2003 ) . Furthermore, a quantitation of the assay would have clearly demonstrated antigen stability.…”