Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects

Wachsman, M.; Petty, Brent G.; Cundy, Kenneth C.; Jaffe, Howard S.; Fisher, P. E.; Pastelak, A.M; Lietman, Paul S.

doi:10.1016/0166-3542(95)00829-2

Cited by 89 publications

(65 citation statements)

References 12 publications

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“…There is no published evidence suggesting that cidofovir has immunosuppressive properties. The main deleterious effect attributed to cidofovir is renal toxicity [12].…”

Section: Discussionmentioning

confidence: 99%

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Smee

Gowen

Wandersee

et al. 2008

International Journal of Antimicrobial Agents

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The causes of death from intranasal cowpox virus infections in mice remain unclear. Hypotheses include severe pneumonitis, hepatitis, and/or hyperproduction of cytokines and chemokines. This work explores these hypotheses by studying the influence of low and high volume virus inoculums on viral pathogenesis. BALB/c mice were infected intranasally with a syncytium-forming variant of cowpox virus in 5-μl or 50-μl volumes containing the same infectious virus challenge dose. The 50-μl infection produced a more rapidly lethal disease associated with severe pneumonitis, high lung and nasal virus titers, and increases in cytokine and chemokine levels in lungs and nasal tissue, while liver infection was minimal. The 5-μl inoculum infection was also lethal, but the infection was primarily confined to the upper respiratory tract, and included elevated nasal cytokine and chemokine levels. The pro-inflammatory cytokine, interleukin-6, was particularly high in both infections. Treatment of the infections with cidofovir (100 mg/kg/day for 2 days starting 24 h after virus exposure) led to survival and suppression of tissue virus titers. Treatment reduced pneumonitis in the 50-μl infection, and lessened cytokine hyperproduction in both infections. We conclude that 5-μl volume inoculum of cowpox virus causes a lethal upper respiratory tract infection, while the 50-μl inoculum targets both upper and lower respiratory tracts, with excessive release of systemic proinflammatory factors occurring. Cidofovir effectively treated both infections and slowed viral replication sufficiently to subdue the exaggerated release of pro-inflammatory mediators.

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“…There is no published evidence suggesting that cidofovir has immunosuppressive properties. The main deleterious effect attributed to cidofovir is renal toxicity [12].…”

Section: Discussionmentioning

confidence: 99%

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Smee

Gowen

Wandersee

et al. 2008

International Journal of Antimicrobial Agents

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“…One Phase 1/11 study (Wachsman et et., 1996) was primarily a pharmacokinetic and bioavailability study to assess the potential utility of oral and subcutaneous routes of cidofovir administration. Oral bioavailability was poor « 5%).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Cidofovir, a New Agent with Potent Anti-Herpesvirus Activity

Hitchcock

Jaffe

Martin

et al. 1996

Antivir Chem Chemother

137

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SummaryCidofovir is a potent, broad spectrum antiviral agent with activity in vitro and in vivo against cytomegalovirus and other members of the herpesvirus family, as well as certain other DNA viruses. After uptake into cells it is converted enzymatically to cidofovir diphosphate, a structural analogue of deoxycytidine triphosphate, which selectively inhibits viral DNA polymerases relative to host cell polymerases. Cross-resistance to cidofovir is not usually seen with human cytomegalovirus isolates that are foscarnet-resistant, or isolates that are ganciclovir-resistant due to a deficiency in ganciclovir phosphorylation. Cross-resistance is seen, however, with isolates that are ganciclovir resistant due to polymerase mutations. A prolonged elimination phase seen in vivo, correlates with a long intracellular half-life seen in vitro and allows for efficacy in-animal models of virus infection with infrequent dosing or prophylaxis. Clinical studies of intravenous cidofovir in cytomegalovirus retinitis in patients with AIDS are claimed to show delay of retinitis progression with maintenance doses given once every 2 weeks.

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“…O cidofovir também pode ser incorporado à porção terminal da cadeia de DNA viral do citomegalovírus (12). Como um mecanismo adicional ou alternativo, esse fár-maco pode ainda inibir a proliferação de células infectadas pelo HPV induzindo a apoptose e sua ação prolongada deve-se ao longo tempo de meia-vida de seus metabólitos ativos, favorecendo uma melhor adaptação posológica através de doses menos frequentes (13 (14).…”

Section: Resultsunclassified

“…O efeito adverso mais pronunciado provocado pelo cidofovir foi a nefrotoxicidade, relatado em 25,6% dos pacientes submetidos a transplante de células-tronco (15), fortemente relacionado à sua ação sistêmica, sendo observado em apenas um único caso relacionado às aplicações intralesionais e tópicas (8,14,15,16). Nessas, por sua vez, podem ocorrer eventuais vermelhidão, ardor e dor local que geralmente desaparecem durante o perío-do de descanso inserido nos ciclos de tratamento tópico (13).…”

Section: Resultsunclassified

Uso Tópico Do Cidofovir Para Tratamento Das Lesões Associadas Ao Papillomavírus Humano: Revisão Da Literatura

Kishishita

Melo

Andrade

et al. 2017

Infarma

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As verrugas genitais são lesões epiteliais induzidas pelo Papillomavirus Humano (HPV). Atualmente, as técnicas utilizadas para tratamento dessas lesões são dolorosas e as recidivas costumam acontecer em um curto espaço de tempo. Diversos estudos têm demonstrado a eficácia do cidofovir no tratamento de HPV entre outras infecções virais. O objetivo desta revisão de literatura é fazer uma abordagem sobre o fármaco e a sua utilização clínica no tratamento de HPV, apresentando a forma farmacêutica, posologia, reações adversas e dados sobre sua eficácia. Os resultados da pesquisa bibliográfica mostram que o uso intralesional e epidérmico do cidofovir em formulações extemporâneas tem se mostrado eficaz no manejo dos condilomas. A utilização tópica do cidofovir se apresenta, portanto, como uma alternativa clínica aos tratamentos convencionais, minimizando os efeitos colaterais locais e evitando a ocorrência de efeitos adversos sistêmicos. Diante disso, faz-se necessária a padronização de uma formulação tópica através de estudos de pré-formulação e demais ensaios clínicos visando a obtenção de uma preparação estável, segura e eficaz para tratamento das lesões associadas ao HPV.

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Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects

Cited by 89 publications

References 12 publications

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Cidofovir, a New Agent with Potent Anti-Herpesvirus Activity

Uso Tópico Do Cidofovir Para Tratamento Das Lesões Associadas Ao Papillomavírus Humano: Revisão Da Literatura

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