Characteristics of the Human Upper Gastrointestinal Contents in the Fasted State Under Hypo- and A-chlorhydric Gastric Conditions Under Conditions of Typical Drug - Drug Interaction Studies.

Chara Litou, Maria Vertzoni, Constantinos Goumas, Vassilis Vasdekis, Wei Xu, Filippos Kesisoglou, Christos Reppas

Journal: Pharmaceutical research 2017;33(6):1399-412

PMID: 26975361

Abstract

OBJECTIVE

Evaluate the impact of reduced gastric acid secretion after administration of two acid-reducing agents on the physicochemical characteristics of contents of upper gastrointestinal lumen of fasted adults.

MATERIALS AND METHODS

Eight healthy male adults, fasted from food for 12 h, participated in a three-phase crossover study. Phase 1: No drug treatment prior to aspirations. Phase 2: Oral administration of 40 mg pantoprazole at ~9 am the last 3 days prior to aspirations and at ~7 am on aspiration day. Phase 3: Oral administration of 20 mg famotidine at ~7 pm prior to aspirations and at ~7 am on aspiration day. Samples from the contents of upper gastrointestinal lumen were aspirated for 50 min, after administration of 240 ml table water at ~9 am.

RESULTS

Reduction of gastric acid secretion was accompanied by reduced buffer capacity, chloride ion concentration, osmolality and surface tension in stomach and by increased pH (up to ~0.7 units) in upper small intestine during the first 50 min post-water administration. The mechanism of reduction of acid secretion seems to be important for the buffer capacity in stomach and for the surface tension in upper gastrointestinal lumen.

CONCLUSIONS

Apart from gastric pH, reduced acid secretion affects physicochemical characteristics of contents of upper gastrointestinal lumen which may be important for the performance of certain drugs/products in the fasted state.

Address: Faculty of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71, Zografou, Greece.; Gastroenterology Department, Red Cross Hospital of Athens, Athens, Greece.; Department of Statistics, Sciences and Technology, Athens University of Economics and Business, Athens, Greece.; Pharmaceutical Sciences and Clinically Supply, Merck & Co, Kenilworth, New Jersey, USA.; Faculty of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71, Zografou, Greece. [email protected].

DOI: 10.1007/s11095-016-1882-8

Link outs

Free resources

Other Literature Sources:

https://scite.ai/reports/26975361

Subscription / membership required

Full Text Sources:

https://doi.org/10.1007/s11095-016-1882-8

MeSH Terms: 2-Pyridinylmethylsulfinylbenzimidazoles, Achlorhydria, Administration, Oral, Adult, Bile Acids and Salts, Buffers, Chlorides, Cross-Over Studies, Drinking, Drug Administration Schedule, Drug Interactions, Famotidine, Fasting, Gastric Acid, Gastric Mucosa, Gastrointestinal Contents, Greece, Healthy Volunteers, Histamine H2 Antagonists, Humans, Hydrogen-Ion Concentration, Male, Osmolar Concentration, Pantoprazole, Proton Pump Inhibitors, Suction, Surface Tension, Time Factors, Young Adult