RESUMEN
The intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 microg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC(0-12 h)) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasma C(max) were 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC(0-12 h) at steady state were 0.274 (95% confidence interval, -0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, -0.06 to 0.08) for d4T-TP:dTTP, and -0.081 (95% confidence interval, -0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.
Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , VIH-1/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Hepatitis C/sangre , Inhibidores de la Transcriptasa Inversa/farmacocinética , Ribavirina/farmacocinética , Adulto , Área Bajo la Curva , Quimioterapia Combinada , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Hepacivirus/fisiología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/sangre , Interferón-alfa/farmacocinética , Lamivudine/sangre , Lamivudine/farmacocinética , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacocinética , Proteínas Recombinantes , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/sangre , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Ribavirina/sangre , Estavudina/sangre , Estavudina/farmacocinética , Factores de Tiempo , Zidovudina/sangre , Zidovudina/farmacocinéticaRESUMEN
A bacterial spore was revived, cultured, and identified from the abdominal contents of extinct bees preserved for 25 to 40 million years in buried Dominican amber. Rigorous surface decontamination of the amber and aseptic procedures were used during the recovery of the bacterium. Several lines of evidence indicated that the isolated bacterium was of ancient origin and not an extant contaminant. The characteristic enzymatic, biochemical, and 16S ribosomal DNA profiles indicated that the ancient bacterium is most closely related to extant Bacillus sphaericus.