5-ETHYL-2'-DEOXYURIDINE

Absorption

Edoxudine cream is able to penetrate the skin in a very rapid manner. This easy penetration allows edoxudine to have a greater activity when compared with other topical antivirals that have better antiviral activity in vitro. In preclinical trials in mice, after intravenous administration of edoxudine, the mean residence time was 25 min. Edoxudine presented a bioavailability of 49% with a Cmax and tmax of 2.4 mcg/g and 31.1 min respectively. The AUC in plasma of edoxudine is significantly higher when administered orally when compared with intravenous administration.

Toxicity

Edoxudine is been reported to present cytotoxic effects and some degree of DNA incorporation in human leukemic cells and PHA-stimulated lymphocytes in vitro.

Chemical properties

Edoxudine is solid

The Uses of 5-ETHYL-2'-DEOXYURIDINE

Edoxudine was found to be a modulator of both antitumor action and pharmacokinetics of 5-Fluorouracil (F596000), a potent antineoplastic agent in clinical use.

The Uses of 5-ETHYL-2'-DEOXYURIDINE

5-Ethyl-2’-deoxyuridine was found to be a modulator of both antitumor action and pharmacokinetics of 5-Fluorouracil (F596000), a potent antineoplastic agent in clinical use.

The Uses of 5-ETHYL-2'-DEOXYURIDINE

antiallergic, mast cell degranulation inhibitor, angiogenesis blocker

Background

Edoxudine is a deoxythymidine analog with activity against herpes simplex virus. It is a potent and selective inhibitor of herpes simplex virus type 1 and 2. The obtained product is an antiviral ointment. The activity of edoxudine against herpes simplex virus was first recognized in 1967. It was later recognized to be effective in vivo in a preclinical model of keratitis caused by herpes virus. It was developed by McNeil Pharmaceutical and approved by Health Canada on December 31, 1992. This medication was later discontinued from the market in 1998.

What are the applications of Application

Edoxudine is a 5-fluorouracil (FU) modulator

Indications

Edoxudine was used in Europe, in the form of a topical antiviral, for the treatment of human herpes keratitis. Human herpes keratitis is an inflammation of the cornea in the eye caused by herpes simplex virus infection. This infection is a cause of significant morbidity whose incidence is significantly increased in the presence of recurrent infection and it can even produce corneal blindness.
Edoxudine 3% cream was also indicated for the treatment of dermal herpes simplex virus. This virus can produce an infection ubiquitously and it is highly contagious. There are two types of herpes virus, type 1 that is mainly transmitted by oral-to-oral contact and type 2 that is sexually transmitted.

Definition

ChEBI: Edoxudine is a pyrimidine 2'-deoxyribonucleoside.

Biochem/physiol Actions

5-Ethyl-2′-deoxyuridine (EUdR) is used as a 5-fluorouracil (FU) modulator. EtdUrd may be used to enhance the therapeutic index of 5-FU by reducing the catabolism, prolonging the plasma and intratumoral concentrations of 5-FU, and offering protection to normal organs by increasing the endogenous uridine levels.

Pharmacokinetics

In reports, it has been indicated that at antivirally active doses, edoxudine is phosphorylated to a much greater extent by hepatitis-infected cells when compared to mock-infected cells. Once phosphorylated, edoxudine is more highly incorporated into viral DNA than cellular DNA. The level of incorporation into viral DNA highly seems to be correlated with the concentration of edoxudine. The suppression of viral DNA synthesis caused a shutoff of viral replication and the viral titration is significantly reduced.The effect of edoxudine is also proven to reduce significantly the lesion area produced by the viral activity to an even 44% reduction.

Metabolism

In preclinical trials it has been reported that edoxudine presents a biotransformation marked by a cleavage of the glycoside bond. The degradation of edoxudine, after oral administration, seems to be processed by the activity of phosphorylases presented in the gastrointestinal tract and by pre-systemic metabolism.