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Cidofovir and Brincidofovir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Graciela Andrei, Robert Snoeck
Brincidofovir (BrinCDV; hexadecyloxypropyl-CDV [HDP-CDV; CMX001]) (see Figure 216.1) was originally designed in response to the need for oral prophylaxis or treatment of smallpox in case variola virus was used as a weapon in bioterrorism. CMX-001 is now being developed by Chimerix, under the name of BrinCDV, for the treatment of a range of viral infections, including smallpox and other DNA viruses. BrinCDV has been given US Food and Drug Administration (FDA) fast track designation to speed development for the prevention of human cytomegalovirus (HCMV), the treatment of adenovirus, and the treatment of smallpox. This drug is currently being evaluated in phase III trials for the prevention of HCMV infection in transplant recipients.
Frequently Asked Questions
Published in Joseph R. Masci, Elizabeth Bass, Ebola, 2017
Joseph R. Masci, Elizabeth Bass
Several drugs interfere with viral replication. These include the following: Ribavirin: This agent has long been used to treat a variety of viral infections, including hepatitis C and respiratory syncytial virus pulmonary infection. Ribavirin has been used successfully in the treatment of hemorrhagic fever viruses, including Lassa fever and Crimean–Congo hemorrhagic fever virus, but has been ineffective in Ebola virus infections.Brincidofovir: Brincidofovir is a prodrug that is metabolized to the antiviral agent cidofovir after cell entry. Cidofovir is active against cytomegalovirus and other DNA herpesviruses and has also been used in the treatment of the JC virus infection progressive multifocal leukoencephalopathy (PML). Despite the fact that Ebola virus is an RNA and not a DNA virus, brincidofovir has been demonstrated to inhibit its replication by an unknown mechanism. Several patients with Ebola were treated in the United States with this drug during the 2014–2016 West Africa epidemics. Although patients treated in the United States and Europe for Ebola infection had a higher rate of recovery than those, in general, treated in Africa, the correlation with outcome in the few patients who received brincidofovir has, so far, not been clear.
The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?
Published in Expert Opinion on Drug Discovery, 2023
Ahmed A. Ezat, Jameel M. Abduljalil, Ahmed M. Elghareib, Ahmed Samir, Abdo A. Elfiky
It is a lipid-conjugate of cidofovir with a higher efficacy in animal models owing to its improved oral bioavailability, lack of nephrotoxicity, and higher conversion rate to the active form [37–39]. The lipid moiety is removed upon entry into the cell via lipid uptake pathways, and the cidofovir becomes available to kinases for phosphorylation reactions. Brincidofovir efficacy was observed in mouse and rabbit models experimentally infected by the mousepox virus and rabbitpox virus, respectively [40–42]. Brincidofovir passed phase III of clinical trials (immunocompromised adults and children were recruited) to treat cytomegalovirus and adenovirus with only a few adverse effects [37]. In the case of a smallpox infection, the recommended dose for adults was 200 mg/week for three weeks [40]. Nonetheless, the efficacy of cidofovir and brincidofovir in MPXV infections is yet to be determined.
Therapeutic strategies to address monkeypox
Published in Expert Review of Anti-infective Therapy, 2022
Brincidofovir (formerly CMX001) is an orally bioavailable lipid acyclic nucleoside phosphonate that is absorbed in the small intestine and transported throughout the body as a phospholipid [27]. Brincidofovir is a lipid conjugate of cidofovir, an antiviral approved for the treatment of cytomegalovirus retinitis in AIDS patients and also has activity against poxviruses, but cidofovir must be administered intravenously and is associated with nephrotoxicity [28]. Brincidofovir, by contrast, has good oral bioavailability, no associated nephrotoxicity, and achieves higher intracellular levels of the active drug compared to cidofovir, making it an appealing agent for the treatment of a variety of infectious diseases [16,29,30]. Brincidofovir has shown activity against double-stranded DNA viruses, including poxviruses such as monkeypox [31–34].
Safety considerations with current and emerging antiviral therapies for cytomegalovirus infection in transplantation
Published in Expert Opinion on Drug Safety, 2019
Guy El Helou, Raymund R Razonable
While myelosuppression is a common adverse effect of all HCMV DNA polymerase inhibitors, nephrotoxicity remains the major adverse effect associated with use of foscarnet and cidofovir. Indeed, it is this toxicity that limits their use as first-line agents for management of HCMV in transplant patients who are already receiving multiple other medications with potential nephrotoxicity. The investigational agent, oral brincidofovir, may circumvent the nephrotoxic effect of cidofovir, but its clinical development has been halted, and initial experience with this drug demonstrated its significant gastrointestinal toxicity that mimicked GVHD. Until clinical trials are performed to demonstrate its safety and efficacy, the authors recommend using brincidofovir only as part of controlled clinical trials. However, these are currently halted.