ST 246

Absorption

Tecovirimat is readily absorbed following oral administration. Following oral administration of 600 mg tecovirimat in healthy adults, the mean steady-state AUC0-24hr was 29816 hr x ng/mL and the Cmax was 2159 ng/mL. Following intravenous administration of 200 mg tecovirimat every 12 hours, the mean steady-state AUC0-24hr was 39405 hr x ng/mL and the Cmax was 2630 ng/mL. The Tmax is about six hours. The steady-state is achieved within four to six days.
The oral bioavailability of tecovirimat is increased when taken with food. A moderate fat and calories meal increased the drug exposure (AUC) by 39% when tecovirimat was orally administered in conjunction with food.

Toxicity

In single-dose toxicity studies, no LD50 has been reached even when tecovirimat was given at very high doses (2000 mg/kg) in mice or non-human primates. There is no clinical experience with overdosage of tecovirimat. In case of overdosage, patients should be monitored for any signs or symptoms of adverse effects. Hemodialysis is not expected to effectively remove tecovirimat in overdosed patients.

The Uses of ST 246

Tecovirimat is an orally bioavailable antipoxvirus compound inhibits extracellular virus formation and protects mice from lethal orthopoxvirus, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses.

Indications

Tecovirimat is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein and is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg. The efficacy of tecovirimat may be reduced in immunocompromised patients. In Europe, it is also indicated to treat complications due to replication of the vaccinia virus following vaccination against smallpox.
In Europe, tecovirimat is also used to treat monkeypox and cowpox in adults and children.

Background

The World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980. However, there have been longstanding concerns that smallpox may be used as a bioweapon. Tecovirimat is an antiviral drug that was identified via a high-throughput screen in 2002. It is effective against all orthopoxviruses, including vaccinia, cowpox, ectromelia, rabbitpox, monkeypox, and Variola (smallpox) virus.
Tecovirimat was approved by the FDA in July 2018 as the first drug ever approved to treat smallpox. Tecovirimat was later approved by Health Canada in December 2021, followed by the approval from the European Commission in January 2022. Other than smallpox, tecovirimat is also indicated to treat complications due to replication of the vaccinia virus following vaccination against smallpox, and to treat monkeypox and cowpox in adults and children. Tecovirimat is available as both oral and intravenous formulations.

Pharmacokinetics

Tecovirimat is an antiviral drug that helps to prevent the spread of virus and reduce viremia. It is effective against all orthopoxviruses tested in vitro, including variola or smallpox virus.

Metabolism

Tecovirimat undergoes hydrolysis mediated by UGT1A1 and UGT1A4. Major metabolites are metabolites M4 (N-{3,5-dioxo-4-azatetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-en-4-yl}amine), M5 (3,5-dioxo-4-aminotetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-ene), and TFMBA (4 (trifluoromethyl) benzoic acid). None of the metabolites is pharmacologically active. None of the glucuronide conjugates was found as a major metabolite in plasma. The exact chemical structures of tecovirimat metabolites have not been fully characterized.