RESUMEN
OBJECTIVE: There is an urgent need to optimize cotreatment for children with tuberculosis and HIV infection. We described nevirapine pharmacokinetics in Zambian children aged less than 3 years, cotreated with nevirapine, lamivudine and stavudine in fixed-dose combination (using WHO weight bands) and rifampicin-based antituberculosis treatment. DESIGN: Twenty-two children received antituberculosis and antiretroviral therapy (ART) concurrently for 4 weeks before pharmacokinetic sampling. Plasma nevirapine concentrations were determined in samples taken immediately before, and 1, 2 and 6 h after an observed dose. Nevirapine pharmacokinetics were compared with those in 16 children aged less than 3 years without tuberculosis. RESULTS: Twenty-two children were treated for HIV/TB coinfection, 10 of whom were girls. One boy was excluded from analysis for nonadherence. The median age was 1.6 years (range: 0.7-3.2). Median weight was 8.0 kg (range: 5.1-10.5). The baseline CD4% was 13.1 (range: 3.9-43.6). Median predose concentration of nevirapine was 2.93 mg/l (range: 1.06-11.4), and peak concentration was 6.33 mg/l (range: 2.61-14.5). The nevirapine AUC up to 12 h was estimated as 52.0 mg.h/l (range: 22.6-159.7) compared with 90.9 mg.h/l (range: 40.4-232.1) in children without tuberculosis (P < 0.001). Predose concentrations of nevirapine were less than 3.0 mg/l in 11 children on tuberculosis treatment versus none of the 16 children without tuberculosis treatment (P = 0.001). AUC was 41% (95% CI: 23-54%) lower in children with tuberculosis than without tuberculosis (P < 0.001) after adjusting for dose per square meter. CONCLUSION: : We found substantial reductions in nevirapine concentrations in young children receiving rifampicin. Further studies are needed to define the pharmacokinetics, safety and efficacy of adjusted doses of nevirapine-based ART in young children with tuberculosis.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Nevirapina/farmacocinética , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/sangre , Antibióticos Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Preescolar , Coinfección , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/metabolismo , Humanos , Lactante , Lamivudine/administración & dosificación , Masculino , Nevirapina/administración & dosificación , Nevirapina/sangre , Rifampin/uso terapéutico , Estavudina/administración & dosificación , Resultado del Tratamiento , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , ZambiaRESUMEN
OBJECTIVE: To investigate the availability of antimalarial agents for the treatment of falciparum malaria in all Dutch hospital pharmacies, including changes in the situation over a period of two years. DESIGN: Descriptive. METHOD: In the period October 2006 to March 2007 all Dutch hospital pharmacies were questioned about the availability of antimalarial agents, by means of a telephone survey. The survey was repeated at the end of 2008. RESULTS: The percentage of hospitals that had quinine in stock increased from 72 (62 of the 86 hospitals responding) to 80 (73 of 91 hospitals). In 2008 artesunate was in stock in 7 hospitals. At the end of 2008 18 Dutch hospitals had no medication available for the treatment of severe malaria tropica; 6 hospitals had no agents for the treatment of malaria at all. CONCLUSION: The ideal situation, in which every hospital in the Netherlands has a supply of adequate agents for the treatment of severe malaria, has not yet been achieved.