The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers

Kamimori, Gary H.; Karyekar, Chetan S.; Otterstetter, Ronald; Cox, Donna S.; Balkin, Thomas J.; Belenky, Gregory; Eddington, Natalie D.

doi:10.1016/s0378-5173(01)00958-9

Cited by 278 publications

(217 citation statements)

References 9 publications

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“…High bioavailability of caffeine in humans and involvement of human P450 1A2 in caffeine metabolism has been reported (Perera et al, 2012;Kamimori et al, 2002). The bioavailability of caffeine in male and female Microminipigs, 79% and 71%, respectively, was similar to the P450 1A-mediated metabolism of caffeine reported in humans (Turpault et al, 2009).…”

Section: Discussionsupporting

confidence: 57%

Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs

et al. 2012

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Section: Discussionsupporting

confidence: 57%

Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs

et al. 2012

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“…21 We repeated this step twice to separately obtain the gPD model parameters for lapse and mean RT statistics.…”

Section: P0(t) = S(t) + κC(t )mentioning

confidence: 99%

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

Ramakrishnan

Wesensten

Kamimori

et al. 2016

Sleep

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Study Objectives: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. Methods: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory-and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). Results: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. Conclusions:The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. Keywords: biomathematical model, caffeine model, chronic sleep restriction, PVT, total sleep deprivation Citation: Ramakrishnan S, Wesensten NJ, Kamimori GH, Moon JE, Balkin TJ, Reifman J. A unified model of performance for predicting the effects of sleep and caffeine. SLEEP 2016;39(10):1827-1841. INTRODUCTIONMathematical models that accurately predict the effects of sleep/wake schedules on human neurobehavioral performance are valuable tools for effective management of operational alertness and fatigue. However, to be of practical use, they must also be able to predict the alertness-and performance-enhancing effects of caffeine, the most widely used stimulant compound. Caffeine is available in a wide range of concentrations in myriad foods and beverages, including coffee, tea, soft drinks, and energy drinks, providing a spectrum of performance-improving effects. Nevertheless, the most thoroughly validated predictive models of performance do not account for the effects of caffeine, 1,2 and the few that do have limitations. For example, the models proposed by Benitez et al. 3 and by Ramakrishnan et al.

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“…The elimination half-life of modafinil is approximately 14 hours (sd = 3.2) with a time to peak concentration of approximately 2 hours (Darwish et al, 2010). For caffeine in gum, the elimination half-life is approximately 2-4 hours (however it varies widely) and the time to peak concentration is approximately 1 hour (45 to 80 min) (Kamimori et al, 2002). Thus, it was expected that caffeine would have a shorter duration of efficacy than would modafinil, and this was taken into account during data analysis and interpretation.…”

Section: Description Of Studymentioning

confidence: 99%

The Effects of Modafinil and OTC Stimulants on Physical and Cognitive Performance

Caldwell¹,

Hartzler²,

Levin³

et al. 2016

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The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers

Cited by 278 publications

References 9 publications

Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs

Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

The Effects of Modafinil and OTC Stimulants on Physical and Cognitive Performance

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