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Food, Acid Supplementation and Drug Absorption – a Complicated Gastric Mix: a Randomized Control Trial

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Abstract

Purpose

The purpose of this study was to determine the impact of food on gastric pH and the ability of over the counter betaine hydrochloride (BHCl) acid to reacidify gastric pH after food-induced elevations in gastric pH.

Methods

This open-label cross over clinical study (NCT02758015) included 9 subjects who were randomly assigned to one of 16 possible, 4-period cross-over sequences to determine the impact and relationship of food and gastric pH with acid supplementation. Subjects were administered various doses (1500 mg, 3000 mg and 4500 mg) of betaine hydrochloride (BHCl) to determine the ability of acid supplementation to reacidify gastric pH after the elevation of gastric pH caused by the ingestion of food.

Results

Following the administration of food and the resulting elevation in gastric pH, time to return to baseline gastric pH levels without acid supplementation was 49.7 ± 14.0 min. Administering 4500 mg of BHCl acid in capsules was able to reacidify gastric pH levels back to baseline following the administration of food in approximately 17.3 ± 5.9 min. AUCpH of each treatment were similar and not statistically different. Mean max pH following the administration of food was 3.20 ± 0.55.

Conclusion

The ability of food to elevate and maintain gastric pH levels in the presence of acid supplementation was made evident throughout the study. A 4500 mg dose of BHCl was required to reacidify gastric pH after the administration of food. This study details the difficulty faced by clinicians in dosing a poorly soluble, weakly basic drug to patients receiving acid reducing agents where administration with food is recommended to avoid gastric side effects.

Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02758015

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Abbreviations

ARA:

Acid reducing agent

BHCl:

Betaine hydrochloride

GERD:

Gastroesophageal reflux disease

PPI:

Proton pump inhibitor

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Acknowledgments and Disclosures

This study was funded by the Benet Fund for Excellence through contributions and through Dr. Benet’s consultation and expert witness fees, as well as Board of Directors remunerations, all of which are made payable to the Regents of the University of California to support the research studies of the Benet Laboratory. The clinical portion of the study was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004. Conflict of Interests: None.

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Authors and Affiliations

  1. School of Pharmacy, University of California San Francisco, San Francisco, CA, USA

    Dalga D. Surofchy

  2. School of Medicine, University of California San Francisco, San Francisco, CA, USA

    Lynda A. Frassetto

  3. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 533 Parnassus Avenue, U-68, San Francisco, 94143-0912, CA, USA

    Leslie Z. Benet

Authors
  1. Dalga D. Surofchy
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  3. Leslie Z. Benet
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Correspondence to Leslie Z. Benet.

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Surofchy, D.D., Frassetto, L.A. & Benet, L.Z. Food, Acid Supplementation and Drug Absorption – a Complicated Gastric Mix: a Randomized Control Trial. Pharm Res 36, 155 (2019). https://doi.org/10.1007/s11095-019-2693-5

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