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

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.

Quantitative analysis of gastrointestinal fluid absorption and secretion to estimate luminal fluid dynamics in rats

“…In recent years, some studies dealing with GI fluid dynamics have not adequately distinguished real fluid movement from apparent fluid movement. The effect of gastric emptying of ingested water and gastric fluid on drug absorption was reported by Grimm et al, while many aspects of intestinal fluid dynamics remain unclear 31 , 32 . In the present study, we analyzed GI fluid dynamics quantitatively from both perspectives (apparent and real) using FD-4 and [ 3 H]water.…”

Determination of Gastric Water Emptying in Fasted and Fed State Conditions Using a Compression-Coated Tablet and Salivary Caffeine Kinetics

“…Similarly, in previous studies with the application of the salivary tracer technique, about 25-35 mg of caffeine were used [13,19,20]. Moreover, a recent study showed no influence of this caffeine labelling on gastric emptying by comparison of MRI data sets [20]. Black iron oxide was used to distinguish the core (black powder) from the coating (white powder) during manufacturing.…”

“…The amount of 25 mg of caffeine used for the determination of gastric emptying is already below the usual dose of caffeine in caffeinated beverages, and thus should not raise concerns about its safety [30] or its pharmacological effect [31,32]. Similarly, in previous studies with the application of the salivary tracer technique, about 25-35 mg of caffeine were used [13,19,20]. Moreover, a recent study showed no influence of this caffeine labelling on gastric emptying by comparison of MRI data sets [20].…”

“…In healthy young volunteers, food is emptied from the stomach slower than water at a rate of about 2-4 kcal/min [46]. Furthermore, this study was performed in an upright position, whereas previous water gastric emptying studies, either in fasted or fed state conditions, have been conducted in a supine position [13,20,26,41,42]. Previous studies in fasted state have shown that changes in posture can have an influence on the intragastric distribution of a drug within the stomach [47,48].…”

“…To distinguish the salivary caffeine concentrations natural 12 C-caffeine was added to the tablet, and stable isotope labelled 13 C 3 -caffeine was added to the ice capsule. The use of a stable isotope to monitor the release and absorption of caffeine measured by caffeine concentrations in saliva has already been applied to a recent study of in vivo oral dosage form disintegration [19], since 12 C-and 13 C 3 -caffeine have similar pharmacokinetic profiles [20].…”