Caffeine is metabolized into more than 25 metabolites in humans, mainly Paraxanthine, Theobromine, and Theophylline
 Caffeine metabolism yields paraxanthine as a final product, which represents 72 to 80% of caffeine metabolism. There are five main metabolic pathways which contribute to caffeine metabolism in adults [13, 14]. The first three consist of demethylization of N-3 to form Paraxanthine, N-1 to form Theophylline
(vasodilator, increased cerebral and muscular blood flow
), and N-7 to form Theophylline (vascular, bronchiole, muscular, and respiratory relaxant). The hepatic cytochrome P-450 (CYP) isoenzyme metabolizes most of the caffeine (95%) by three demethylizations which on average give an in vivo metabolism percentage of 85% paraxanthine, 10% theobromine, and 5% theophylline . The fourth pathway results in the formation of uracil metabolites, and the fifth consists of renal elimination of the remaining percentage of caffeine that was not able to be degraded in the process. The large interindividual differences observed in plasmatic concentration of caffeine following the administration of an equal dose are mainly due to variations in metabolism. These variations depend on four factors: genetic polymorphisms, metabolic induction and inhibition of cytochrome P-450, individual (weight, sex), and the presence of hepatic diseases  Caffeine is absorbed rapidly and completely from the intestinal tract, making it 100% bioavailable. The time in which maximum plasmatic concentration is obtained (Tmax) is 30–45 minutes [11, 14, 16, 17] fasting and is delayed with food ingestion; it has an average metabolic half life in humans of 2.5 to 4.5 hours 
Caffeine, by acting on the VSMC, generates a minimal initial contraction and then a significant vasodilator effect. There are various mechanisms that explain these effects.
Caffeine, by competitively blocking the adenosine receptors
, increases its plasmatic concentration  which increases its systemic effects. At a systemic level, adenosine stimulates the chemoreceptor distributed throughout the circulation, causing a generalized increase in sympathetic tone, with an increase in circulating catecholamines, peripheral vascular resistance, and renin secretion [44, 65]. Several studies have documented an increase in systolic arterial pressure of 6 to 7.5 mmHg and 2.6 to 4 mmHg in diastolic pressure 60 minutes after the administration of 300 mg of caffeine (equivalent to drinking a triple espresso) [18, 43]. In spite of this “indirect” vasoconstrictor effect produced by caffeine, it is important to point out that the chronic consumption of caffeine creates a tolerance to its adenosine receptor-dependent effects. Chronic blocking of the adenosine receptors, inducing “upregulation” (an increase in the number and sensitivity) of the receptors has been described with a low-moderate caffeine consumption (approximately two cups of coffee for more than 5 days) .