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

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://ichgcp.net/clinical-trials-registry/NCT02758015.

Keywords: betaine hydrochloride; gastric pH; gastric reacidification; meal effects.

Conflict of interest statement

Conflict of Interests: None

Figures

Fig 1

The gastric pH vs time plot for a sample patient from each treatment arm: food only, 1500mg of BHCl, 3000mg of BHCl and 4500mg of BHCl.

Fig 2.

Figure 2a depicts the mean time to baseline for comparison 1 with the standard deviations shown as error bars. The calculation of time to baseline was determined from the time of administration of BHCl until the gastric-pH had reached the baseline levels. In the food only arm of comparison 1, the time began at the administration of food. Figure 2b illustrates the difference between group means with 90% confidence interval error bars.

Fig 3.

Figure 3a depicts the mean time to baseline for comparison 2 with the standard deviations shown as error bars. The calculation of time to baseline was determined from the time of administration of BHCl until the gastric-pH had reached the baseline levels. In the food only arm of comparison 2, the starting time point was 15-minutes after the administration of food. Figure 3b illustrates the difference between group means with 90% confidence interval error bars.