Plasma Caffeine Concentrations Research Articles

Ergogenic Effects of Caffeine Consumption in a 3-min All-Out Arm Crank Test in Paraplegic and Tetraplegic Compared With Able-Bodied Individuals.

The aim of our study was to investigate the effect of caffeine supplementation on 3-min all-out arm crank exercise performance in paraplegic (P) and tetraplegic (T) compared with able-bodied (AB) participants. A placebo-controlled, randomized, crossover, and double-blind study design was chosen to investigate the differences between caffeine (CAF) and placebo (PLC). In total, 34 healthy, trained participants were tested. Seventeen were AB (median [minimum; maximum] VO2peak: 33.9 mL/min/kg [23.6; 57.6]), 10 were P (VO2peak: 34.4 mL/min/kg [19.5; 48.8]), and 7 were T (VO2peak: 13.6 mL/min/kg [8.6; 16.3]). All participants performed two 3-min all-out tests on an arm crank ergometer following the ingestion of either PLC or CAF. Power output parameters, plasma caffeine (PC), epinephrine (EPI), and norepinephrine (NOR) concentrations were assessed. CAF significantly increased average power over the first 30 s (p = .028) and 60 s (p = .005) in P, but not in T (p = .61; p = .87) nor in AB (p = .25; p = .44). Peak power was increased in the CAF trial in AB (+46 W) as well as in P (+21 W) but was not significantly different from PLC (AB: p = .10; P: p = .17). PC significantly increased in all groups (AB: p = .002; P: p = .005; T: p = .018) whereas EPI showed a significant increase only in AB (p = .002) and in P (p = .018). NOR increased significantly in AB (p = .018) but did not increase in the other groups. Caffeine seems to enhance short-duration exercise performance in P. In contrast, T showed a high interindividual variability and overall no ergogenic effect was detected in this group.

Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus)

1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg−1, respectively, to four male common marmosets were investigated.2. The plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner that approximated those as reported for pharmacokinetics in humans.3. Bioavailabilities were ∼100% for caffeine and warfarin, but <25% for omeprazole and metoprolol. Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1′-hydroxylation as evident in the recombinant system.4. These results suggest that common marmosets, despite their rapid clearance of some human P450 probe substrates, could be an experimental model for humans and that marmoset P450s have functional characteristics that differ from those of human and/or cynomolgus monkey P450s in some aspects, indicating their importance in modeling in P450-dependent drug metabolism studies in marmosets and of further studies.

Prediction of plasma caffeine concentrations in young adolescents following ingestion of caffeinated energy drinks: a Monte Carlo simulation.

These data indicate that CED ingestion can increase the risk of serious caffeine intoxication in young adolescents, particularly those with low body mass. • Excessive consumption of caffeine can lead to serious caffeine intoxication. • The risk of potential harmful caffeine intoxication after ingestion of caffeinated energy drinks (CED) has not been adequately evaluated in adolescents. • Predicted maximal plasma caffeine concentration profiles of adolescents with lower body weights showed an overlap with the ingested caffeine concentrations obtained from documented fatalities. • The present simulation-based pharmacokinetic analysis demonstrates that CED ingestion could lead to potentially serious caffeine intoxication in this cohort.

PP.16.18

Objective: In rats, high sodium intake augments adenosine-induced vasodilation (Liclican EL et al. 2005 and Dobrowolski L et al. 2007). This study tests the hypothesis that the acute blood pressure response to caffeinated coffee (adenosine receptor antagonist) is augmented by high sodium intake in humans. Design and method: 13 healthy volunteers (8 male) used low (LS; 6 gram/24 hours) and high (HS; 12 gram/24 hours) salt diet in random order, each for 5 days with 4 day wash-out. At the end of each diet and after 24 hours of caffeine abstinence, subjects drank 350 ml of caffeinated coffee. Primary endpoint was the blood pressure response (Dinamap 1846 SX; Critikon, Portanje Electronica BV) to coffee. Results: Maintenance to the diet was confirmed by urinary sodium excretion (5 ± 2 (SD) versus 12 ± 4 g NaCl/24 hours, p < 0,0001). Plasma caffeine concentration significantly increased from 0.2 ± 0.2 (SD) to 6.6 ± 1.8 μg/ml (p > 0.3 for comparison between 2 days, paired t-test). Table: Course in blood pressure (mean ± SEM (mmHg)*p < 0.05 versus low salt; #p < 0.01 for increase over time. The interaction between high and low sodium diet and caffeine intake on SBP, DBP (p > 0,3) and MAP (p > 0,05) was not statistically significant (ANOVA for repeated measures). SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; MAP: Mean Arterial Blood Pressure. Conclusions: High sodium intake does not augment the acute blood pressure response to coffee. This observation does not support a mitigating role of adenosine on the salt-associated increase in blood pressure in humans.

Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations

Development of formulations and drug delivery strategies for paediatric use is challenging, partially due to the age ranges within this population, resulting in varying requirements to achieve optimised patient outcomes. Although the oral route of drug delivery remains the preferred option, there are problematic issues, such as difficulty swallowing and palatability of medicines specific to this population. The parenteral route is not well accepted by children due to needle-related fear and pain. Accordingly, a plethora of alternative routes of drug administration have been investigated. Microneedles (MN) breach the stratum corneum (SC), the outermost layer of skin, increasing the number of drug substances amenable to transdermal delivery. This strategy involves the use of micron-sized needles to painlessly, and without drawing blood, create transient aqueous conduits in the SC. In this study, polymeric dissolving MN and hydrogel-forming MN were fabricated incorporating two model drugs commonly used in paediatric patients (caffeine and lidocaine hydrochloride). The potential efficacy of these MN for paediatric dosing was investigated via in vitro and in vivo studies. Views pertaining to MN technology were sought amongst school children in Northern Ireland, members of the UK general public and UK-based paediatricians, to determine perceived benefits, acceptance, barriers and concerns for adoption of this technology. In this study, polymeric MN were shown to substantially enhance skin permeability of the model therapeutic molecules in vitro and in vivo. In particular, hydrogel-forming MN led to a 6.1-fold increase in caffeine delivery whilst lidocaine HCl delivery was increased by 3.3-fold using dissolving MN in vitro. Application of caffeine-loaded MN led to a caffeine plasma concentration of 23.87μg/mL in rats at 24h. This research also highlighted a strong consensus regarding MN technology amongst schoolchildren, paediatricians and the general public, regarding potential use of MN in the paediatric population. Overall, 93.6% of general public respondents and 85.9% of paediatricians regarded the use of MN as a positive approach.

The Effect of Caffeine Ingestion during Evening Exercise on Subsequent Sleep Quality in Females.

In a randomised, double-blind, placebo-controlled crossover design, 10 females taking monophasic oral contraceptives completed 90 min intermittent treadmill-running 45 min after ingestion of 6 mg∙kg(-1) body mass anhydrous caffeine or artificial sweetener (placebo). Water (3 mL∙kg(-1)) was provided every 15 min during exercise. Venous blood samples were taken before, during and after exercise, as well as after sleep (~15 h post-ingestion), and levels of caffeine, paraxanthine, theobromine and theophylline were measured using high-performance liquid chromatography. Sleep quality was assessed using the Leeds Sleep Evaluation Questionnaire. Plasma caffeine concentration peaked 100 min after ingestion. Caffeine clearance was 0.95±0.14 mL·min(-1)·kg(-1) while the elimination half-life of caffeine was 17.63±8.06 h. Paraxanthine and theophylline levels were significantly elevated at 15 h with no significant change in theobromine. Sleep latency and subsequent quality of sleep was impaired following caffeine supplementation (P<0.05); there were no differences between trials for how participants were feeling upon awakening. This is the first controlled study to examine caffeine supplementation on sleep quality in female athletes taking a low-dose monophasic oral contraceptive steroid following an intermittent-exercise running protocol. The data shows that female athletes using monophasic oral contraceptive steroids will have impaired sleep quality following evening caffeine ingestion.

In vitro-to-in vivo correlation of the skin penetration, liver clearance and hepatotoxicity of caffeine

This work illustrates the use of Physiologically-Based Toxicokinetic (PBTK) modelling for the healthy Caucasian population in in vitro-to-in vivo correlation of kinetic measures of caffeine skin penetration and liver clearance (based on literature experiments), as well as dose metrics of caffeine-induced measured HepaRG toxicity. We applied a simple correlation factor to quantify the in vitro and in vivo differences in the amount of caffeine permeated through the skin and concentration-time profiles of caffeine in the liver. We developed a multi-scale computational approach by linking the PBTK model with a Virtual Cell-Based Assay to relate an external oral and dermal dose with the measured in vitro HepaRG cell viability. The results revealed higher in vivo skin permeation profiles than those determined in vitro using identical exposure conditions. Liver clearance of caffeine derived from in vitro metabolism rates was found to be much slower than the optimised in vivo clearance with respect to caffeine plasma concentrations. Finally, HepaRG cell viability was shown to remain almost unchanged for external caffeine doses of 5–400 mg for both oral and dermal absorption routes. We modelled single exposure to caffeine only.

Age-related changes of hepatic clearances of cytochrome P450 probes, midazolam and R-/S-warfarin in combination with caffeine, omeprazole and metoprolol in cynomolgus monkeys using in vitro–in vivo correlation

1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) were investigated after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg−1, respectively, in combination to three young (3-year-old) and three aged (16-year-old) cynomolgus monkeys.2. The plasma concentrations of caffeine and R-/S-warfarin decreased slowly in a monophasic manner, but those of omeprazole, metoprolol and midazolam decreased rapidly, in a similar manner to those as reported for pharmacokinetics in humans.3. The mean maximum concentrations of R- and S-warfarin (4.6 and 3.7 µg/mL, respectively) in aged monkeys after oral administration were significantly higher than those in young monkeys (3.3 and 2.7 µg/mL). The mean clearance (CL) values of midazolam in aged monkeys (9.5 mL/min/kg) were significantly lower than those in young monkeys (13 mL/min/kg).4. Individual intrinsic CL values for omeprazole (r = 0.29) and metoprolol (r = 0.30) of individual monkey livers were inversely correlated with their ages significantly (p < 0.05) in liver microsomes prepared from 55 cynomolgus monkeys.5. These results suggest that cynomolgus monkeys could be a good model for humans, especially with particular characteristics in reduced CLs of some human P450 substrates by aging.

Improvements on neuromuscular performance with caffeine ingestion depend on the time-of-day.

To determine whether the ergogenic effects of caffeine ingestion on neuromuscular performance are similar when ingestion takes place in the morning and in the afternoon. Double blind, cross-over, randomized, placebo controlled design. Thirteen resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75% and 90% 1RM), at maximal velocity. Trials took place 60 min after ingesting either 6 mg kg(-1) of caffeine or placebo. Two trials took place in the morning (AMPLAC and AMCAFF) and two in the afternoon (PMPLAC and PMCAFF), all separated by 36-48 h. Tympanic temperature, plasma caffeine concentration and side-effects were measured. Plasma caffeine increased similarly during AMCAFF and PMCAFF. Tympanic temperature was lower in the mornings without caffeine effects (36.7±0.4 vs. 37.0±0.5°C for AM vs. PM; p<0.05). AMCAFF increased propulsive velocity above AMPLAC to levels similar to those found in the PM trials for the 25%, 50%, 75% 1RM loads in the SQ exercise (5.4-8.1%; p<0.05). However, in the PM trials, caffeine ingestion did not improve propulsive velocity at any load during BP or SQ. The negative side effects of caffeine were more prevalent in the afternoon trials (13 vs. 26%). The ingestion of a moderate dose of caffeine counteracts the muscle contraction velocity declines observed in the morning against a wide range of loads. Caffeine effects are more evident in the lower body musculature. Evening caffeine ingestion not only has little effect on neuromuscular performance, but increases the rate of negative side-effects reported.

Plasma lactate concentration as an indicator of plasma caffeine concentration in acute caffeine poisoning.

Severe caffeine poisoning is rare, but is associated with high mortality. Plasma caffeine concentration is one of the indications of treatment of caffeine poisoning; however, it is not easily measured at most emergency departments. If the plasma lactate concentration and the plasma caffeine concentration were correlated, the plasma lactate concentration may be an indication of caffeine poisoning. In this study, we investigated the correlation between the plasma lactate concentration and the plasma caffeine concentration. From April 2010 to March 2012, 18 patients with severe caffeine poisoning by overdose were admitted at our Emergency Center. The plasma lactate concentration and plasma caffeine concentration of 10 patients were determined at the same time at 12-24 h after admission. These findings were plotted and we analyzed the correlation and trends in these concentrations. There were strong correlations between the plasma lactate concentration and the plasma caffeine concentration at admission (n = 18) and at 12-24 h after admission (n = 10) (correlation coefficients, 0.95 and 0.91, respectively). There was a strong positive correlation between the trend of the plasma lactate concentration and the plasma caffeine concentration (n = 10). The correlation coefficient was 0.91. These results are extremely beneficial for emergency department clinical physicians because such findings permit the determination of the severe caffeine poisoning patient. Additionally, the plasma lactate concentration might be one of the indicators of hospitalization and discharge.

The Effect of a Caffeinated Mouth-Rinse on Endurance Cycling Time-Trial Performance

The purpose of this study was to investigate if acute caffeine exposure via mouth-rinse improved endurance cycling time-trial performance in well-trained cyclists. It was hypothesized that caffeine exposure at the mouth would enhance endurance cycling time-trial performance. Ten well-trained male cyclists (mean ± SD: 32.9 ± 7.5 years, 74.7 ± 5.3 kg, 176.8 ± 5.1cm, VO₂peak = 59.8 ± 3.5 ml·kg⁻¹·min⁻¹) completed two experimental time-trials following 24 hr of dietary and exercise standardization. A randomized, double-blind, placebo-controlled, cross-over design was employed whereby cyclists completed a time-trial in the fastest time possible, which was equivalent work to cycling at 75% of peak aerobic power output for 60 min. Cyclists were administered 25 ml mouth-rinses for 10 s containing either placebo or 35 mg of anhydrous caffeine eight times throughout the time-trial. Perceptual and physiological variables were recorded throughout. No significant improvement in time-trial performance was observed with caffeine (3918 ± 243 s) compared with placebo mouth-rinse (3940 ± 227 s). No elevation in plasma caffeine was detected due to the mouth-rinse conditions. Caffeine mouth-rinse had no significant effect on rating of perceived exertion, heart rate, rate of oxygen consumption or blood lactate concentration. Eight exposures of a 35 mg dose of caffeine at the buccal cavity for 10s does not significantly enhance endurance cycling time-trial performance, nor does it elevate plasma caffeine concentration.

Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography–tandem mass spectrometry

A rapid, sensitive, simple and accurate LC–MS/MS method for the simultaneous quantitation of caffeine, and its three primary metabolites, theobromine, paraxanthine, and theophylline, in rat plasma was developed and validated. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column using 1μg/mL acetaminophen as an internal standard. Each sample was run at 0.5mL/min for a total run time of 7min/sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization. The lower limit of quantification was 5ng/mL for all analytes with linear ranges up to 5000ng/mL for caffeine and 1000ng/mL for its metabolites. The coefficient of variation for assay precision was less than 12.6%, with an accuracy of 93.5–114%. The assay was successfully applied to determine plasma concentrations of caffeine, theobromine, paraxanthine, and theophylline in rat administered various energy drinks containing the same caffeine content. Various energy drinks exhibited considerable variability in the pharmacokinetic profiles of caffeine and its three primary metabolites, even containing the same caffeine. Different additives of energy drinks might contribute to these results.

A Preliminary Study on the Effects of Self-Reported Dietary Caffeine on Pain Experience and Postoperative Analgesia.

Caffeine reduces the amount of analgesic medications necessary to provide postoperative pain (POP) relief and augments treatments for headaches and dental pain. Despite considerable evidence of its beneficial effects, little is understood about the role of dietary caffeine consumption on baseline pain sensitivity or POP following oral surgery. Baseline experimental pain testing (quantitative sensory testing [QST]) using four stimulus modalities was conducted on 30 healthy adults (53% females) before surgical extraction of four third molars. Self-reported caffeine ingestion was reported before QST, and on the day of surgery, preoperative and postoperative caffeine plasma concentrations (CPC) were measured by mass spectrometry. POP ratings were obtained at timed intervals. In QST, compared to subjects who self-reported no caffeine intake, those who self-reported caffeine ingestion demonstrated a higher pain sensitivity, particularly, on ramp and hold sustained heat at 44°C and 46°C, as well as a lower heat pain threshold and tolerance (p=0.05). Differences approached significance (p=0.06) in POP between subjects with CPC above 300 ng/mL and those with CPC below 300 ng/mL. Specifically, those with >300 ng/mL CPC had a slightly lower POP (mean 2.43, range 0-5) compared to those with <300 ng/mL CPC whose POP ratings were slightly higher (mean 2.89) with a greater variability (range 0-9.5). Self-reported, dietary caffeine intake was associated with higher QST ratings with lower threshold and tolerance particularly on heat pain modalities. External factors (i.e., analgesic dosage) may have played a role in the analgesic effects of caffeine on POP in oral surgery, especially in individuals with CPC exceeding 300 ng/mL who reported lower pain.

Caffeine Occupancy of Human Cerebral A1 Adenosine Receptors: In Vivo Quantification with 18F-CPFPX and PET

Caffeine is the neuroactive agent in coffee and tea and is a broadly consumed stimulant. It is a nonselective antagonist of the neuromodulator adenosine and, if applied in commonly consumed doses, evokes its stimulating effects through the blockade of adenosine receptors. (18)F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ((18)F-CPFPX) has been established as a highly selective and affine PET ligand for the A(1) adenosine receptor (A(1)AR). The objective of the present study was to visualize and quantify the in vivo occupancy of the human cerebral A(1)AR by caffeine using (18)F-CPFPX and PET. Fifteen subjects (age range, 24-68 y) underwent a 140-min bolus-plus-constant-infusion PET experiment after at least 36 h of caffeine abstinence. Metabolite-corrected blood data were used to calculate steady-state distribution volumes (V(T)) during the baseline condition of the scan between 70 and 90 min. Subsequently, subjects received a 10-min infusion of varying concentrations (0.5-4.3 mg/kg of body weight) of caffeine at 90 min. Occupancy V(T) of the A(1)AR was thereafter estimated using data acquired between 120 and 140 min. Occupancy levels were calculated using the Lassen plot, from which the inhibitory concentrations of 50% were derived. Plasma levels of caffeine were determined at regular intervals. One subject received an intravenous vehicle as a placebo. Caffeine displaced 5%-44% of (18)F-CPFPX binding in a concentration-dependent manner. There was no change of radioligand binding after the administration of placebo. Half-maximal displacement was achieved at a plasma caffeine concentration of 67 μM, which corresponds to 450 mg in a 70-kg subject or approximately 4.5 cups of coffee. Given a biologic half-life of about 5 h, caffeine might therefore occupy up to 50% of the cerebral A(1)AR when caffeinated beverages are repeatedly consumed during a day. Furthermore, the present study provides evidence that (18)F-CPFPX PET is suitable for studying the cerebral actions of caffeine, the most popular neurostimulant worldwide.

Effects of Morning Caffeine’ Ingestion on Mood States, Simple Reaction Time, and Short-Term Maximal Performance on Elite Judoists

The purpose of the present study was to evaluate the ergogenic effect of caffeine ingestion on mood state, simple reaction time, and muscle power during the Wingate test recorded in the morning on elite Judoists. TWELVE ELITE JUDOISTS (AGE: 21.08 ± 1.16 years, body mass: 83.75 ± 20.2 kg, height: 1.76 ±6.57 m) participated in this study. Mood states, simple reaction time, and muscle power during the Wingate test were measured during two test sessions at 07:00 h and after placebo or caffeine ingestion (i.e. 5 mg/kg). Plasma concentrations of caffeine were measured before (T0) and 1-h after caffeine' ingestion (T1) and after the Wingate test (T3). Our results revealed an increase of the anxiety and the vigor (P<0.01), a reduction of the simple reaction time (P<0.001) and an improvement of the peak and mean powers during the Wingate test. However, the fatigue index during this test was unaffected by the caffeine ingestion. In addition, plasma concentration of caffeine was significantly higher at T1 in comparison with T0. In conclusion, the results of this study suggest that morning caffeine ingestion has ergogenic properties with the potential to benefit performance, increase anxiety and vigor, and decrease the simple reaction time.

Caffeine and Sprinting Performance

The aims of this study were to evaluate the effects of caffeine supplementation on sprint cycling performance and to determine if there was a dose-response effect. Using a randomized, double-blind, placebo-controlled design, 17 well-trained men (age: 24 ± 6 years, height: 1.82 ± 0.06 m, and body mass(bm): 82.2 ± 6.9 kg) completed 7 maximal 10-second sprint trials on an electromagnetically braked cycle ergometer. Apart from trial 1 (familiarization), all the trials involved subjects ingesting a gelatine capsule containing either caffeine or placebo (maltodextrin) 1 hour before each sprint. To examine dose-response effects, caffeine doses of 2, 4, 6, 8, and 10 mg·kg bm(-1) were used. There were no significant (p ≥ 0.05) differences in baseline measures of plasma caffeine concentration before each trial (grand mean: 0.14 ± 0.28 μg·ml(-1)). There was, however, a significant supplement × time interaction (p < 0.001), with larger caffeine doses producing higher postsupplementation plasma caffeine levels. In comparison with placebo, caffeine had no significant effect on peak power (p = 0.11), mean power (p = 0.55), or time to peak power (p = 0.17). There was also no significant effect of supplementation on pretrial blood lactate (p = 0.58), but there was a significant time effect (p = 0.001), with blood lactate reducing over the 50 minute postsupplementation rest period from 1.29 ± 0.36 to 1.06 ± 0.33 mmol·L(-1). The results of this study show that caffeine supplementation has no effect on short-duration sprint cycling performance, irrespective of the dosage used.

Caffeine Supplementation Had No Effect on Endurance Capacity in Elderly Subjects Who Had Abstained from Caffeine-Containing Nutrition for 8 Hours

Background: In this study, we investigated the effect of acute caffeine ingestion on physical performance after only 8 hours of caffeine abstinence. Methods: The study was a randomized, double-blind, cross-over study and included 30 healthy subject aged ≥70 years who had been recruited by their general practitioner. The participants abstained from caffeine for 8 hours (overnight) and the next morning they received placebo and then caffeine (6 mg/kg), or caffeine and then placebo at an interval of 1 week. One hour after the intervention we measured cycling endurance (ergometer), perceived effort during cycling (Borg scale), postural stability (force platform), and maximal isometric arm flexion strength and endurance (dynamometer chair). Blood samples were taken before the intervention, before cycling, after 5 minutes of cycling, and at exhaustion. Results: The participants had a usual coffee intake of six cups/day and after 8 hours of caffeine abstinence the plasma concentration of caffeine was 4.1 μM. Caf...

Caffeine And Sprinting Performance: Dose Responses And Efficacy

PURPOSE: The aims of this study were to evaluate the effects of caffeine supplementation on short-duration sprint cycling performance and to determine if there was a dose-response effect. METHODS: Using a randomised, double-blind, placebo-controlled design, 17 well-trained males (means ± standard deviation for age, height, body mass, and body fat of the subjects were: 24 ± 6 years, 1.82 ± 0.06 m, 82.2 ± 6.9 kg, and 13.5 ± 3.4%, respectively) completed seven maximal 10 s sprint trials on an electromagnetically-braked cycle ergometer, with a minimum of 48 hours between trials. Apart from Trial 1, which was used for familiarisation purposes, all trials required subjects to ingest a gelatine capsule containing either caffeine or placebo (maltodextrin) one hour prior to performing each sprint. To examine dose-response effects, the following doses of caffeine were used: 2, 4, 6, 8, and 10 mg·kg-1. RESULTS: The absence of significant differences in baseline measures of plasma caffeine concentration (established via high performance liquid chromatography) (grand mean: 0.14 ± 0.28 μg·ml-1; p = 0.30) confirmed subject compliance with caffeine abstinence prior to each trial. There was, as anticipated, a significant supplement × time interaction (p < 0.001) with larger caffeine doses producing higher post-supplementation plasma caffeine levels. In comparison with placebo, the results revealed no significant effect of supplementation on peak power (grand mean: 1135 ± 192 W; p = 0.11), mean power (grand mean: 774 ± 111 W; p = 0.55), or time to peak power (grand mean: 4.45 ± 1.16 s; p = 0.17). CONCLUSION: In contrast with the established benefits of caffeine supplementation on endurance performance, the results of this study show that caffeine supplementation has no effect on short-duration sprint cycling performance, irrespective of the dosage used.

Clinical and Physiological Correlates of Caffeine and Caffeine Metabolites in Primary Insomnia

To explore the relationship between plasma concentrations of caffeine and subjective and polysomnographic measures of sleep in both good sleeper controls (GSC) and individuals with primary insomnia (PI), following the consumption of low-moderate quantities of caffeine in the home environment. 65 PI and 29 GSC, each consuming < 4 four coffee cup equivalents of caffeine daily, were recruited. Subjects completed a diary detailing sleep habits and caffeine consumption, one night of polysomnography, and a blood sample for measurement of plasma caffeine and its metabolites at bedtime. Plasma concentrations of caffeine, its primary metabolite, paraxanthine, and other metabolites were determined for each subject and correlated with self-report and polysomnographic measures. No statistically significant differences were found between GSC and PI with respect to number of caffeinated beverages consumed (p = 0.91), estimated absolute caffeine ingestion (p = 0.48), time of caffeine consumption (p = 0.22), or plasma concentrations of caffeine (p = 0.92) or paraxanthine (p = 0.88). Significant correlations were found between plasma concentrations of caffeine/paraxanthine and endorsed caffeine intake (r = 0.58, p < 0.05) and estimated absolute caffeine ingestion (r = 0.57, p < 0.05). Plasma caffeine/paraxanthine was significantly correlated with percent stage 1 sleep (r = 0.32, p < 0.05). However, plasma concentrations of caffeine/paraxanthine were not significantly correlated with other subjective or polysomnographic measures of sleep disturbance in either GSC or PI. These data suggest that low-moderate amounts of caffeine consumed in the home environment, and mostly during morning hours, have little effect on subjective or polysomnographic measures of sleep in GSC or PI.

Influences of immobilization and footshock stress on pharmacokinetics of theophylline and caffeine in rats.

The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg-1) and caffeine (30 mg kg-1) administered orally were examined in rats. The immobilization stress for 30 min or 1 h immediately after oral administration caused marked immobilization period-related decreases in plasma theophylline concentrations during the absorption phase, but did not affect plasma caffeine concentrations. The ka and Cmax values for theophylline were significantly decreased, and the tmax was significantly increased. On the other hand, when the immobilization stress was loaded for 1 or 3 h before the oral administration, the plasma theophylline or caffeine concentrations were not affected. The footshock stress for 30 min immediately after oral administration did not significantly decrease plasma theophylline concentrations during the absorption phase. These results suggest that the pharmacokinetics of theophylline are influenced by strong stress, possibly due to the inhibition of its absorption from the gastrointestinal tract, but the pharmacokinetics of caffeine are not influenced by stress, probably due to its central action.