Trifluridine

Overview

Trifluridine (also called trifluorothymidine; abbreviation TFT or FTD) is an anti-herpesvirus antiviral drug, used primarily as prescription eyedrops. It was sold under the trade name Viroptic by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is now wholly owned by King Pharmaceuticals.[1] WP

Trifluridine was approved for medical use in 1980. It is also a component of the anti-cancer drug trifluridine/tipiracil, which is taken by mouth.[2] WP

Uses, dosage and effects

Medical uses

Trifluridine eye drops are used for the treatment of keratitis and keratoconjunctivitis caused by the herpes simplex virus types 1 and 2, as well as for prevention and treatment of vaccinia virus infections of the eye.[3] WP

A Cochrane Systematic Review showed that trifluridine and aciclovir were a more effective treatment than idoxuridine or vidarabine, significantly increasing the relative number of successfully healed eyes in one to two weeks.[4] WP

Risks and side effects

Adverse effects

Common side effects of trifluridine eye drops include transient burning, stinging, local irritation, and edema of the eyelids.[3] WP

Adverse effects of the anti-cancer formulation have only been evaluated for the combination trifluridine/tipiracil, not for the individual components. WP⚠ Wikipedia itself has flagged this text: citation needed.

Interactions

Interactions

Only in vitro interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2). Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine. Being a thymidine phosphorylase inhibitor, trifluridine could also interact with substrates of this enzyme such as zidovudine.[5] WP

For the eye drops, trifluridine absorption is negligible, rendering interactions basically irrelevant.[3] WP

Pharmacology

Mechanism of action (eye drops)

It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the –CF₃ group added to the uracil component blocks base pairing, thus interfering with viral DNA replication. WP⚠ Wikipedia itself has flagged this text: citation needed.

Pharmacokinetics (eye drops)

Trifluridine passes the cornea and is found in the aqueous humour. Systemic absorption is negligible.[3] WP

Pharmacokinetics (oral)

Pharmacokinetic data of oral trifluridine have only been evaluated in combination with tipiracil, which significantly affects biotransformation of the former. At least 57% of trifluridine are absorbed from the gut, and highest blood plasma concentrations are reached after two hours in cancer patients. The substance has no tendency to accumulate in the body. Plasma protein binding is over 96%. Trifluridine is metabolised by the enzyme thymidine phosphorylase to 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTY), and also by glucuronidation. Elimination half-life is 1.4 hours on the first day and increases to 2.1 hours on the twelfth day. It is mainly excreted via the kidneys.[5] WP

Tipiracil causes Cₘₐₓ (highest blood plasma concentrations) of trifluridine to increase 22-fold, and its area under the curve 37-fold, by inhibiting thymidine phosphorylase.[5] WP

Chemistry

Formula

C10H11F3N2O5 PC

CAS number

70-00-8 PC

Molar mass (g/mol)

296.20 PC

IUPAC name (computed by PubChem)

1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione PC

SMILES

C1[C@@H]([C@H](O[C@H]1N2C=C(C(=O)NC2=O)C(F)(F)F)CO)O PC

InChIKey

VSQQQLOSPVPRAZ-RRKCRQDMSA-N PC

PubChem CID

6256

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Patel AK, Abhyankar R, Brais LK, Duh MS, Barghout VE, Huynh L, Yenikomshian MA, Ng K, Fuchs CS. Trifluridine/Tipiracil and Regorafenib in Patients with Metastatic Colorectal Cancer: A Retrospective Study at a Tertiary Oncology Center. The Oncologist. December 2021. doi:10.1002/onco.13942 · PMID 34406678 · PMC8649060
2. Other Kimberlin DW. Principles and Practice of Pediatric Infectious Disease. 2012
3. Other Trifluridine
4. Journal / agency Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. The Cochrane Database of Systematic Reviews. January 2015. doi:10.1002/14651858.CD002898.pub5 · PMID 25879115 · PMC4443501
5. Other Austria-Codex. 2015

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.