Step-by-step explanation:After ingestion, caffeine is quickly absorbed from the gastrointestinal tract into the circulatory system [17, 18]. The maximum plasma concentration is reached after 30-60 minutes from consumption. However, maximum plasma concentrations reached between 15 and 120 min have been reported, due to inter-individual differences and delayed gastric emptying. Caffeine is widely distributed through the body. The pre-systemic (i.e., first-pass) metabolism takes place in the liver, since orally ingested substances are absorbed through the small intestine into the portal circulation, before entering the systemic one. Caffeine’s pre-systemic metabolism is negligible [17] and, once caffeine is absorbed, it promptly gets into all the body tissues and crosses the blood-brain, blood-placenta, and blood-testis barriers [17, 19]. The hepatic microsomal enzyme system is in charge of caffeine metabolism in the liver.