ABSTRACT
Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.
Subject(s)
Humans , Male , Female , Child , Adult , Middle Aged , Anti-HIV Agents/pharmacokinetics , Antimetabolites/pharmacokinetics , Lamivudine/pharmacokinetics , Leukocytes, Mononuclear/metabolism , Reverse Transcriptase Inhibitors/pharmacokinetics , Zidovudine/pharmacokinetics , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/blood , Antimetabolites/administration & dosage , Antimetabolites/blood , Cells, Cultured , Chromatography, High Pressure Liquid , Clinical Trials as Topic , HIV Infections/drug therapy , Lamivudine/administration & dosage , Lamivudine/blood , Phosphates/metabolism , Phosphorylation , Polyphosphates/metabolism , Radioimmunoassay , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/blood , Time Factors , Zidovudine/administration & dosage , Zidovudine/bloodABSTRACT
El exceso de filtración por falla valvular y más tardíamente por la formación de fibrosis ha motivado el diseño de nuevos instrumentos que alcancen mejor eficacia. El presente estudio trata de 14 ojos de 13 pacientes con glaucoma de difícil control, refractarios a cualquier tratamietno instituido. Se analiza este nuevo producto, valorando los resultados a pronto, mediano y largo plazo. Se observan las ventajas que se obtienen al implantar un mecanismo valvular y los resultados.