The deuterium kinetic isotope effect has been used to affect the cytochrome P450 metabolism of the deuterated versions of substances. This study compares the pharmacokinetics of caffeine, a Generally Recognized As Safe food and beverage ingredient, versus d9-caffeine, a potential caffeine alternative, and their respective metabolites at two dose levels in 20 healthy adults. A single dose of 50 mg or 250 mg of caffeine, or a molar-equivalent dose of d9-caffeine, were orally administered in solution with blood samples collected for up to 48 h post-dose. Plasma concentrations of parent and metabolites were analyzed using validated LC-MS/MS methods. Both d9-caffeine and caffeine were rapidly absorbed; however, d9-caffeine exhibited a higher (ca. 29%-43%) C and 4-5-fold higher AUC than caffeine, and lower C, lower AUC, and a 5-10-fold reduction in the relative exposure to the active metabolites of caffeine. Results were consistent in normal and rapid metabolizers, and both substances were well tolerated.
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| http://dx.doi.org/10.1016/j.yrtph.2022.105194 | DOI Listing |
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