Estimation of gastric pH in cynomolgus monkeys, rats, and dogs using [13C]-calcium carbonate breath test

Tobita, Kazuki; Inada, Makoto; Sato, Asuka; Sudoh, Kimiyoshi; Sato, Hitoshi

doi:10.1016/j.dld.2016.06.022

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…Interestingly, some studies have reported that the calcium carbonate breath test (CBT) is useful for estimating changes in gastric acid secretion. (23,24) CBT is a non-invasive test, as the subjects are administered 13 C-labeled calcium carbonate (Ca 13 CO 3 ) orally; subsequently, the amount of 13 C-labeled carbon dioxide ( 13 CO 2 ) in the breath (produced upon reaction with the gastric acid) is analyzed.…”

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confidence: 99%

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test

Miyamoto

Tsuda

Kato

et al. 2019

J. Clin. Biochem. Nutr.

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Vonoprazan, a potassium-competitive acid blocker, is a new class of acid-suppressing agent. The acid-inhibitory effect of vonoprazan has been well-documented. However, there is no report on the extent to which the amount of gastric acid secretion is suppressed, not pH measurement, by the use of vonoprazan. The aim of this study was to evaluate this suppression effect. This was a single-arm, interventional pilot study involving 7 healthy Japanese men. The subjects were administered 20 mg vonoprazan for 6 days. The amount of gastric acid secretion was determined using the calcium carbonate breath test. The acid outputs were defined as the maximum Δ13C‰ (Δ13C max) and area under the curve (AUC) during the 30 min sampling period. The Δ13C max and AUC values significantly decreased on the administration of 20 mg vonoprazan. The AUC dropped by approximately 78% on day 1 and by 84% on day 6 and subsequently returned to the control level after cessation of vonoprazan therapy (reduction by 68% on day 7 and by 42% on day 8). In conclusion, the amount of gastric acid secretion rapidly decreased by the administration of vonoprazan; this inhibitory effect was found to be potent and long-lasting. (UMIN ID: UMIN000025469)

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Section: Introductionmentioning

confidence: 99%

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test

Miyamoto

Tsuda

Kato

et al. 2019

J. Clin. Biochem. Nutr.

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“…The use of 13 C-labeled probes for assessment of in vivo metabolic activity has been extensively studied by our research group. 16,[21][22][23] In particular, we have demonstrated the utility of the 13 C-EM breath test for the quick and noninvasive evaluation of CYP3A-mediated drug interactions in vivo. 16 As summarized in Table 4, the AUCs of the 13 C breath response decreased by approximately half in the CBD-NE coadministration groups (10 and 50 mg/kg) compared with the control, indicating suppression of 13 C-EM metabolism due to CBD-mediated inhibition of CYP3A.…”

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confidence: 99%

Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition In Vivo in Rats

Nagao

Nakano

Tajima

et al. 2020

Cannabis and Cannabinoid Research

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Introduction: Cannabidiol (CBD) is known to affect the pharmacokinetics of other drugs through metabolic inhibition of CYP2C19 and CYP3A4. However, there is a lack of in vivo evidence for such drug interactions. Therefore, we investigated the saturability of CBD metabolism and CBD-drug interactions through inhibition of CYP3A in vivo. Materials and Methods: A nanoemulsion formulation of CBD (CBD-NE) was orally administered to rats at doses of 5, 10, 25, and 50 mg/kg, and plasma concentrations of CBD were measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to examine the dose-dependency of CBD exposure (area under the curve [AUC]). To examine the effect of a CYP3A inhibitor on CBD pharmacokinetics, rats were orally pretreated with 50 mg/kg ketoconazole (KCZ), a strong CYP3A inhibitor, before oral administration of CBD-NE at doses of 10 and 50 mg/kg, and plasma concentrations of CBD were measured using LC-MS/MS. Moreover, 13 C-erythromycin was orally administered following administration of either NE (without CBD), as a control, or CBD-NE at 1, 10, and 50 mg/kg, and 13 C-breath response was measured by using an infrared analyzer. Results: After administration of various doses of the nanoemulsified CBD formulation to rats, the exposure of CBD (i.e., the AUC calculated from the plasma concentration-time profile) increased in a greater than doseproportional manner, especially at doses above 10 mg/kg. The AUC and maximum plasma concentration (C max) of CBD after oral administration of CBD-NE (10 mg/kg) increased approximately three times by the coadministration of KCZ. Moreover, according to the CBD-induced changes of 13 C-breath response, the metabolism of 13 C-erythromycin was shown to be inhibited by CBD at doses of 10 and 50 mg/kg, but not at 1 mg/kg. Conclusions: Nonlinear disposition and CYP-mediated drug interactions of CBD at doses exceeding 10 mg/kg were demonstrated for the first time in vivo in rats. Given the present results, it is proposed that caution for dosedependent drug interactions should be considered for CBD.

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Estimation of gastric pH in cynomolgus monkeys, rats, and dogs using [13C]-calcium carbonate breath test

Cited by 2 publications

References 15 publications

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test

Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test

Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition In Vivo in Rats

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