Antiviral agent cidofovir

Antiviral Efficacy and Clinical Use. Cidofovir (Vis-tide) is used primarily to treat CMV retinitis in people with AIDS.111 When used clinically, this drug is often combined with probenecid, an agent that inhibits renal excretion of cidofovir, thereby providing higher plasma levels of this antiviral agent.112... 

The treatment for smallpox is primarily supportive. Research is ongoing into antiviral therapies for smallpox but currently therapy for patients infected with smallpox remains supportive, with intravenous fluids, pain medications, and antibiotics as needed for secondary bacterial infections (Henderson, 1999). Cidofovir, an antiviral agent used primarily against cytomegalovirus infection, has shown some promise against orthopox viruses such as vaccinia and cowpox in animal studies (De Clercq, 2002). Currently it is approved in its IV form for use in the treatment of adverse effects of smallpox vaccination (CDC, 2003). 

Alternative antiviral agents for the treatment of drug-resistant herpesviruses are the acyclic nucleoside phosphonate analogs. The lead compound of this new series of antiviral molecules is cidofovir [(S)-l-(3-hydroxy-2-phosphonylmethoxypropyljcytosine] (HPMPC), which has a broad-spectrum antiviral activity in vitro and in vivo against several DNA viruses. Cidofovir has been approved for the treatment of CMV retinitis in AIDS patients, and it has also been shown to be effective in the treatment of persistent mucocutaneous infections caused by ACVr HSV and ACVr/PFAr HSV (6,7). 

Cidofovir is an antiviral agent that inhibits viral DNA synthesis by interfering with viral DNA polymerase. It is indicated in the treatment of Cytomegalovirus retinitis in patients with AIDS. Cidofovir (l-[(5)-3-hydroxy-2-(phosphonomethoxy)-propyljcytosine dihydrate) is a cytidine nucleotide analog with inhibitory activity against human herpes, papilloma, polyoma, pox, and adenoviruses. 

Adefovir and cidofovir are clinically important antiviral agents and have been shown to cause drug-associated nephrotoxicity in some patients. In vitro studies demonstrated that adefovir and cidofovir were about 500 and 400-fold more cytotoxic, respectively, in OAT 1-transfected CHO cells compared to the vector control transfected CHO cells, suggesting that the drug associated nephrotoxicity could be caused by OAT 1-mediated accumulation of adefovir and cidofovir in renal proximal tubules (Ho et al., 2000). 

Figure 2.20 Cidofovir as a reference standard for antiviral agent.

Hitchcock MJM, Jaffe HS, Martin JC, Stagg RJ. Cidofovir, a new agent with potent anti-herpes virus activity. Antiviral Chem Chemother 1996 7 115-127. 

Huggins JW, Marteniz MJ, Zaucha GM, Jahrling PB, Smee D, Bray, M. 1998. The DNA Polymerase Inhibitor Cidofovir (HPMC, Vistide) is a Potential Antiviral Therapeutic Agent for the Treatment Of Monkeypox And Other Orthopox Virus Infections. Presented at the XII International Poxvirus Symposium, St Thomas, VI, June 6-10. 

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