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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

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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.

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Abbreviations

API:

Active pharmaceutical ingredient

BIC:

Bayesian information criterion

DDI:

Drug-drug interaction

FaSSIF:

Fasted state simulating intestinal fluid

FMT:

Famotidine

GC:

Glycocholic acid

GCDC:

Glycochenodeoxycholic acid

GDC:

Glycodeoxycholic acid

GI:

Gastrointestinal

H2-RA:

Histamine-2 receptor antagonist

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HPLC:

High performance liquid chromatography

Lyso-PC:

Lyso-phosphatidylcholine

MG:

Monoglyceride

PC:

Phosphatidylcholine

PNT:

Pantoprazole

PPI:

Proton pump inhibitor

SD:

Standard deviation

TC:

Taurocholic acid

TCDC:

Taurochenodeoxycholic acid

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ACKNOWLEDGMENTS AND DISCLOSURES

This work would not have been possible without the participation of reliable volunteers and authors would like to express their sincere appreciation. Authors would like to thank Dr Aikaterini Lourbakou and Ms Mirofora Kotoglou for their excellent assistance during intubations and Prof. Michael Koupparis, Department of Chemistry, NKUA, for his assistance in the viscosity measurements. Part of the present work was presented as a poster at AAPS Annual Meeting, October 25–29, 2015, Orlando, Florida, USA.

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    Authors and Affiliations

    1. Faculty of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71, Zografou, Greece

      Chara Litou, Maria Vertzoni & Christos Reppas

    2. Gastroenterology Department, Red Cross Hospital of Athens, Athens, Greece

      Constantinos Goumas

    3. Department of Statistics, Sciences and Technology, Athens University of Economics and Business, Athens, Greece

      Vassilis Vasdekis

    4. Pharmaceutical Sciences and Clinically Supply, Merck & Co, Kenilworth, New Jersey, USA

      Wei Xu & Filippos Kesisoglou

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    1. Chara Litou
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    2. Maria Vertzoni
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    Correspondence to Christos Reppas.

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    Chara Litou and Maria Vertzoni contributed equally to this work.

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    Litou, C., Vertzoni, M., Goumas, C. et al. 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. Pharm Res 33, 1399–1412 (2016). https://doi.org/10.1007/s11095-016-1882-8

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

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