A Comprehensive Monograph on Tegafur: Pharmacology, Clinical Application, and Therapeutic Context

Executive Summary

Tegafur is an orally bioavailable antineoplastic agent that functions as a prodrug of the widely used chemotherapeutic, 5-fluorouracil (5-FU). Developed to overcome the poor oral bioavailability and pharmacokinetic unpredictability of 5-FU, Tegafur’s clinical significance is realized almost exclusively through its incorporation into sophisticated combination drug products. These formulations, namely Tegafur/uracil (UFT) and Tegafur/gimeracil/oteracil (commercially known as S-1 or Teysuno), are rationally designed to modulate the pharmacology of 5-FU, enhancing its therapeutic index by increasing its systemic exposure while mitigating its characteristic toxicities.[1]

The primary mechanism of action involves the hepatic conversion of Tegafur to 5-FU, which then inhibits thymidylate synthase, a critical enzyme in the DNA synthesis pathway, leading to cell death.[1] The co-formulated agents in UFT and S-1 strategically inhibit dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for 5-FU degradation, thereby prolonging its activity. S-1 further includes a gastrointestinal-protective agent that locally reduces 5-FU activation in the gut mucosa, decreasing common side effects like diarrhea and mucositis.[2]