Edoxudine

256.26

256.26

239-226-1

15ZQM81Y3R

DTXSID4045890

C87662

D - Dermatologicals

29349990

99.1

-1.09

1.389±0.06 g/cm3(Predicted)

152.5 °C

1.569

H2O: >38.4 mcg/ml

-20°C

9.98

NONH for all modes of transport

3

YU7500000

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

The plasma protein binding of edoxudine is very low and it is reported to be of about 7%. It is mainly found in a bound state to albumin.

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.

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.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)

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.|This pharmacokinetic property is not available.|The plasma clearance of edoxudine is reported to be 85 ml/min.

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.

In preclinical trials on mice, after intravenous administration, edoxudine presented a very short distribution half-life of 1.4 min. In the same trials, the elimination half-life was reported to be of 24.1 min.

Edoxudine is a potent inhibitor of the replication of herpes simplex virus type 1 and 2. For the activation of this drug, the action of viral thymidine kinase is required to phosphorylate this molecule in order to form the 5'-monophosphate derivative. Then, it is needed to be further phosphorylated by cellular enzymes until the formation of the 5'-triphosphate derivative which is a competitive inhibitor of the viral-coded DNA polymerase. The advantage of edoxudine is that it is highly selective, this characteristic can be seen by its preferential phosphorylation in herpes-infected cells and its preferential incorporation into viral DNA.

1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil