The last puzzle in acetylsalicylic acid biotransformation: New achievements in metabolism

The history of salicylates began four millennia ago. Salicylates were used for centuries in the form of a herbal drug – willow bark. Isolation of salicin started in 1829, followed by the fi rst synthesis in 1857. It took four decades to fi nd the acetylated form of salicylic acid that could be obtained as a pure substance. Aspirin was born in 1897. Salicylates were unique drugs in many ways. Th e fi rst clinical trial was conducted in 1763 and confi rmed the antipyretic activity of willow bark. In 1899, clinical trials confi rmed the benefi cial eff ects of aspirin, granting aspirin the status of a panacea (universal remedy). Owing to its analgesic, antipyretic, anti-infl ammatory and antithrombotic properties, aspirin is one of the most widely used drugs today. Every fi fth adult takes aspirin on a daily basis, and every second person aged 65 and above. Th e metabolism of aspirin is revisited in this paper, highlighting the latest achievements in researching its metabolic fate. Hydrolysis, glucuronidation and glycine conjugation, as major metabolic reactions, are covered accompanied with the minor metabolic pathway of aromatic hydroxylation. Addition of human cytochromes P450 completes the biotransformation scheme of (acetyl)salicylic acid.