DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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2 resultados
Resultados da Pesquisa
Item Novel insights to enhance therapeutics with acyclovir in the management of herpes simplex encephalitis.(2021) Assis, Maria Silvia Gurgel; Pedrosa, Taciane Cristina Fernandes; Moraes, Fernanda Segurasse de; Caldeira, Tamires Guedes; Pereira, Gislaine Ribeiro; Souza, Jacqueline de; Ruela, Andre Luís MoraisAcyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg1 8-hourly in adults with normal renal function. However, the mortality related to HSE treated with acyclovir remains high (~20%) and permanent sequelae are commonly reported after 1 year (~50%). This review analyzed clinical trials following IV acyclovir administration. Novel insights aiming to improve drug bioavailability were reviewed, including acyclovir or its prodrugs, leading to the systemic distribution of the drug or drug targeting. Much research effort has been made to improve antiviral therapy, searching for delivery systems increasing acyclovir bioavailability by non-invasive pathways, such as oral and nasal pathways, or parenterally administered nanotechnology-based systems leading to drug targeting. Nanocarriers administered by non-invasive pathways represent feasible alternatives to treat HSE, even though not be industrially manufactured yet.Item Comparison of bidirectional lamivudine and zidovudine transport using MDCK, MDCK-MDR1, and Caco-2 cell monolayers.(2009) Souza, Jacqueline de; Benet, Leslie Z.; Huang, Yong; Storpirtis, SílviaBidirectional transport studies were conducted using Caco-2, MDCK, and MDCK–MDR1 to determine P-gp influences in lamivudine and zidovudine permeability and evaluate if zidovudine permeability changes with the increase of zidovudine concentration and/or by association of lamivudine. Transport of lamivudine and zidovudine separated and coadministrated across monolayers based on these cells were quantified using LC–MS–MS. Drug efflux by P-gp was inhibited using GG918. Bidirectional transport of lamivudine and zidovudine was performed across MDCK–MDR1 and Caco-2 cells. Statistically significant transport decrease in B!A direction was observed using MDCK–MDR1 for zidovudine and MDCK–MDR1 and Caco-2 for lamivudine. Results show increased transport in B!A and A!B directions as concentration increases but data from Papp increase in both directions for both drugs in Caco-2, decrease in MDCK, and does not change significantly in MDCK–MDR1. Zidovudine transport in A!B direction increases when coadministrated with increasing lamivudine concentration but does not change significantly in B!A direction. Zidovudine and lamivudine are P-gp substrates, but results assume that P-gp does not affect significantly lamivudine and zidovudine. Their transport in monolayers based on Caco-2 cells increase proportionally to concentration (in both directions) and zidovudine transport in Caco-2 cell monolayer does not show significant changes with lamivudine increasing concentrations.