Pharmacology Trifluridine/tipiracil

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mechanism of action. details see text.


the drug consists of cytotoxin trifluridine , thymidine phosphorylase inhibitor (tpi) tipiracil. trifluridine incorporated dna during dna synthesis , inhibits tumor cell growth. trifluridine (tft) incorporated dna phosphorylation thymidylate kinase (tk) tf-tmp; tf-tmp covalently binds tyrosine 146 of active site of thymidylate synthase (ts) inhibiting enzyme s activity. ts vital synthesis of dna because enzyme involved in synthesis of deoxynucleotide, thymidine triphosphate (dttp). inhibition of ts depletes cell of dttp , causes accumulation of deoxyuridine monophosphate (dump), increases likelihood uracil gets misincorporated dna. also, subsequent phosphorylations of tf-tmp cause increased level of tf-ttp within cell, results in being incorporated dna. though exact mechanism of how tft causes dna damage not understood, hypothesized incorporation tf-ttp in dna leads dna strand break formation.


tipiracil prevents degradation of trifluridine via thymidine phosphorylase (tp) when taken orally , has antiangiogenic properties. not has thymidine phosphorylase been shown identical platelet-derived endothelial cell growth factor (pd-ecgf), endogenous factor involved in formation of new vasculature, products of enzyme may contribute stimulation of endothelial cell chemotaxis.


pharmacokinetics

see trifluridine#pharmacokinetics (oral) , tipiracil#pharmacokinetics.








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