ABSTRACT
BACKGROUND & OBJECTIVE: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. METHODS: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV-positive individuals with CD4 cell counts>350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. RESULTS: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. INTERPRETATION & CONCLUSION: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies.
Subject(s)
Adult , Antitubercular Agents/urine , CD4-Positive T-Lymphocytes/drug effects , Drug Administration Schedule , Drug Resistance , HIV Infections/complications , HIV Seropositivity , Humans , Immunocompromised Host , Isoniazid/urine , Middle Aged , Models, Biological , Rifampin/urine , Tuberculosis/complications , Xylose/chemistryABSTRACT
Foi investigado o fenótipo acetilador de isoniazida em 23 pacientes caucasóides com cirrose hepática, por intermédio da avaliaçäo do percentual de acetilisoniazida na urina. A proporçäo de acetiladores lentos entre cirróticos foi bem menor que aquela verificada em um grupo controle de caucasóides. Ao se separar os pacientes quanto ao grau de insuficiência hepática, os dados mostraram que a acetilaçäo da isoniazida é tanto mais lenta quanto maior é a insuficiência hepática. Concluiu-se que a cirrose afeta a capacidade hepática de acetilaçäo da isoniazida, alterando o fenótipo acetilador desse medicamento
Subject(s)
Humans , Isoniazid/metabolism , Liver Cirrhosis/metabolism , Phenotype , Isoniazid/urine , Acetylation , Liver Cirrhosis/urine , Liver/metabolismABSTRACT
O fenótipo acetilador da isoniazida foi investigada em 19 pacientes caucasóides portadores de síndrome de Gilbert, por intermédio da avaliaçäo do percentual de acetil-isoniazida na urina. A proporçäo de acetiladores lentos entre os pacientes com síndrome de Gilbert foi semelhante àquela verificada em um grupo controle de caucasóides. Conclui-se que na síndrome de Gilbert näo há interferência na capacidade hepática de acetilaçäo da isoniazida