Interrelations between plasma caffeine concentrations and neurobehavioural effects in healthy volunteers: model analysis using NONMEM.

The objective was to develop a population pharmacokinetic-pharmacodynamic model of caffeine's psychomotor effects in healthy, non-habitual users of caffeine. Twenty Chinese males each received a single dose of 250 mg of caffeine orally. Plasma concentrations of caffeine were determined at various times within 24 h after dosing. The subjects' psychomotor performance was evaluated before and at various times after dosing by a test battery consisting of oculomotor assessment (saccadic velocity) as well as the computerised Swedish Performance Evaluation System. Nonlinear mixed-effects modelling to analyse the pharmacokinetic-pharmacodynamic relationships was performed using NONMEM. Model robustness was assessed by a nonparametric bootstrap. The results showed that caffeine caused significant improvements in psychomotor functioning. The time course of these effects was best described by pharmacokinetic/pharmacodynamic models involving an effect compartment. The transfer half-lives between plasma and effect site for different domains of psychomotor functioning were in the range 24.8-49.5 min. Evaluation of the final models showed close agreement between pairs of bootstrapped and final model parameter estimates (all differences<10%). These results provided the first suggestive evidence that caffeine effects on psychomotor performance occur after some time delay relative to changes in plasma caffeine concentration. The models for the neurobehavioural tests provided similar transfer half-lives between plasma and effect site.

Effects of two and five days of creatine loading on muscular strength and anaerobic power in trained athletes.

The purpose of this study was to establish the effects of 2 and 5 days of creatine loading, coupled with resistance training, on muscular strength and anaerobic performance in trained athletes. Seventeen trained men were randomly assigned to a creatine or a placebo group. The creatine supplementation group consumed 20 g of creatine per day (4 doses of 5 g per day), whereas the placebo group was given a placebo similar in appearance and taste over the 5-day supplementation duration. Anaerobic power and strength performance measures, in addition to blood and urine analysis, were conducted in the morning before the supplementation began and on the third and sixth day to establish the effect of 2 and 5 days of creatine loading, respectively. The study found that a 5-day creatine loading regime coupled with resistance training resulted in significant improvements in both average anaerobic power, as measured by the 30-second Wingate test and back squat strength compared with just training alone. However, 2 days of supplementation was not sufficient to produce similar performance gains as that observed at the end of 5 days of loading in trained men, despite increases in creatine uptake in the body. The standard 5-day loading regime should hence be prescribed to individuals supplementing with creatine for enhanced strength and power.