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. 2023 Jan 18;15(2):328.
doi: 10.3390/pharmaceutics15020328.

Comparing Salivary Caffeine Kinetics of 13C and 12C Caffeine for Gastric Emptying of 50 mL Water

Michael Grimm  1 , Adrian Rump  1 , Lisa Meilicke  1 , Maximilian Feldmüller  2 , Rebecca Keßler  3 , Eberhard Scheuch  4 , Mladen Vassilev Tzvetkov  4 , Werner Weitschies  1
Affiliations

Comparing Salivary Caffeine Kinetics of 13C and 12C Caffeine for Gastric Emptying of 50 mL Water

Michael Grimm et al. Pharmaceutics. .

Abstract

Gastric water emptying as a critical parameter for oral drug absorption can be investigated by several imaging techniques or by the interpretation of pharmacokinetics of appropriate substances. Recently introduced salivary caffeine kinetics is a valuable tool, but the required caffeine abstinence limits its applicability. To avoid the caffeine abstinence, stable isotope-labeled caffeine might be used, but the representability and transferability of kinetics for evaluation of gastric emptying must be demonstrated. Thus, salivary caffeine pharmacokinetics were compared for naturally occurring 12C-caffeine and 13C3-caffeine after the administration of water under fasting conditions in six healthy young subjects. For this purpose, an ice capsule containing the two caffeine species was administered with 50 mL tap water. Gastric water emptying was simultaneously quantified using magnetic resonance imaging (MRI). Gastric emptying of 50 mL of water could be successfully evaluated. The salivary caffeine kinetics of 13C3- and 12C-caffeine were nearly congruent and showed good linear correlations in all subjects, with a mean correlation coefficient of 0.96 in pooled data. Thus, the substitution of natural 12C caffeine with stable isotope-labeled 13C3-caffeine offers the opportunity for broader application of the salivary caffeine gastric emptying technique and increases the robustness of the method against environmental contamination with caffeine.

Keywords: UNGAP; caffeine; gastric emptying; magnetic resonance imaging (MRI); saliva tracers; stable isotopes.

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Conflict of interest statement

M.G., A.R., L.M., R.K., E.S., M.T. and W.W. are only affiliated with the University of Greifswald and declare no conflicts of interest. M.F. is now an employee of Bayer AG, but the company was not involved in the study design, conduction or evaluation. M.F. also declares no conflicts of interest.

Figures

Figure 1
Figure 1
Individual relative gastric emptying (blue) and salivary 12C-caffeine concentrations (black) before and after intake of 35 mg caffeine with 50 mL of water.
Figure 2
Figure 2
Mean ± SD salivary concentrations of 12C-caffeine, 13C3-caffeine and the individual linear correlation of the respective concentrations from six volunteers after administration of an ice capsule containing 35 mg 12C-caffeine and 35 mg 13C3-caffeine together with 50 mL tap water.
Figure 3
Figure 3
Individual salivary caffeine concentrations of 12C-caffeine (black) and 13C3-caffeine (red) on the left side and their linear correlation on the right side from subjects 001, 002 and 003.
Figure 4
Figure 4
Individual salivary caffeine concentrations of 12C-caffeine (black) and 13C3-caffeine (red) on the left side and their linear correlation on the right side from subjects 004, 005 and 006.
Figure 5
Figure 5
Gastric volume curves after intake of 240 mL of water with 35 mg caffeine (black) and without caffeine (grey) from literature [2,36,37].
See this image and copyright information in PMC

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