Comparative Pharmacokinetics of a Novel, Patented Sustained Release Caffeine Versus Immediate Release Caffeine and Their Effects on Alertness & Mood

Abstract

\n \n \n Oral caffeine consumption results in rapid absorption with high blood levels followed by its sharp decline and is typically associated with reduction in beneficial effects of caffeine. To help extend the benefits of caffeine over a six-eight hour time period, we developed a new sustained release caffeine (SRC) formulation called XtenergyTM. The primary study objective was to compare the pharmacokinetic profile of SRC with immediate release caffeine (IRC). Secondary objectives were comparing the effects of SRC and IRC using caffeine research visual analogue scales (Caff - VAS) and evaluate its safety.\n \n \n \n Twenty-six subjects were randomized to receive 200\xa0mg of caffeine from SRC and IRC in a double blind, single-dose, two-period, crossover study in healthy subjects under fasting state. A washout duration of 7 days was followed between the two periods. Blood samples were collected at –4, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 & 24 hours in each period. Plasma caffeine levels were analysed using a validated LCMS/MS method. The changes in Caff-VAS for relaxed, alert, jittery, tired, tense, headache & overall mood from baseline (0) to 1, 2, 4, 6, 8, 10 & 12\xa0hrs were evaluated.\n \n \n \n Twenty-four male subjects with mean age 32.71\xa0±\xa06.18\xa0yrs completed the study. Median tmax was 325.53% higher (4.00 vs 0.94\xa0hrs) and mean t1/2 was 21.34% higher (9.24\xa0± 4.56 vs 7.61\xa0±\xa03.98\xa0hrs) for SRC (P\xa0<\xa00.05) compared to IRC, respectively. Geometric least squares means (GLSM) for AUC4–8 (11,673.52 vs 10,930.25 hr.ng/mL) & AUC6–12 (14,043.79 vs 11,432.41 hr.ng/mL) were 6.80% and 22.84% higher for SRC compared to IRC, respectively. SRC showed an equivalent total absorption as IRC based on 90% CI for AUC0–24 (43,312.07 vs 44,009.64 hr*ng/mL). SRC demonstrated significant effects (P\xa0<\xa00.05) on feelings of being more alert, less tired, better overall mood, less jittery & less tense compared to IRC. SRC was well tolerated with no adverse events.\n \n \n \n The SRC formulation resulted in slow & sustained levels of plasma caffeine associated with feelings of being more alert, less tired, better overall mood, less jittery and less tense for longer time periods without any safety concerns. SRC could be beneficial for those involved in sustained operations demanding peak cognitive & physical performance for a longer time.\n \n \n \n OmniActive Health Technologies Ltd.\n