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Gastric pH and Gastric Residence Time in Fasted and Fed Conscious Cynomolgus Monkeys Using the Bravo® pH System

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Abstract

Purpose

To measure fasted and fed gastric pH and gastric residence time (GRT) in Cynomolgus monkeys using Bravo® radiotelemetry capsules.

Methods

Continuous pH measurements were recorded with Bravo® capsules, which were either attached to the monkeys’ stomach or administered as free capsules. Meals (either slurry or standard), were administered at designated times with monkeys chair-restrained during slurry meal ingestion.

Results

From the attached capsule studies, the fasted gastric pH (∼1.9–2.2) was consistent among monkeys. Under fasted conditions, pH spikes were infrequently observed (once every 7.9 min to 3.6 h) with peaks reaching pH 9.4 and having short durations (<1 min). After feeding, the gastric pH rose quickly and remained alkaline for approximately 4.5–7.5 h before returning to baseline. Although significantly different (p < 0.05), there was overlap between the fasted (153 ± 87 min) and fed (436 ± 265 (slurry) and 697 ± 193 (standard) min) GRT due to considerable inter- and intra-subject variability.

Conclusions

Fasted gastric pH was similar between monkeys and literature human values. After a meal, the monkey gastric pH was elevated for a longer duration than that in human. The monkey GRT appears longer than that observed in human under both fasted and fed conditions, although this is likely dependent on the Bravo® capsule size.

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Abbreviations

ANOVA:

analysis of variance

FDA:

Food and Drug Administration

GERD:

gastroesophageal reflux disease

GRT:

gastric residence time

IQR:

interquartile range

MMC:

migrating myoelectrical complex

Q1 :

25% quartile

Q3 :

75% quartile

RMSE:

root mean squared error

SD:

standard deviation

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Acknowledgments

We would like to thank Wendy Morrison, Jennifer Gilbride and summer student, Howard Wu from the Department of Drug Metabolism and Pharmacokinetics and Robert Roache, Bob Lynch, Katrina Rivera, Earl Jenkins, Debra Paul and Laura Flanagan from the department of Laboratory Animal Sciences for providing technical assistance. Also, thanks to Simon Zhuang from Biomedical Data Sciences for providing statistical support.

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Author notes

  1. Kelly M. Mahar Doan

    Present address: Department of Clinical Pharmacokinetics Modeling and Simulation, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, 709 Swedeland Rd., King of Prussia, Pennsylvania, 19406, USA

Authors and Affiliations

  1. Department of Preclinical Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, 709 Swedeland Rd., King of Prussia, Pennsylvania, 19406, USA

    Emile P. Chen, Kelly M. Mahar Doan, Samm Portelli & Wei Shi

  2. Department of Laboratory Animal Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA

    Robert Coatney & Vernal Vaden

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  1. Emile P. Chen
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Correspondence to Emile P. Chen.

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Chen, E.P., Mahar Doan, K.M., Portelli, S. et al. Gastric pH and Gastric Residence Time in Fasted and Fed Conscious Cynomolgus Monkeys Using the Bravo® pH System. Pharm Res 25, 123–134 (2008). https://doi.org/10.1007/s11095-007-9358-5

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  • DOI: https://doi.org/10.1007/s11095-007-9358-5

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