Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
Clarithromycin
+ Rifabutin
+ Sulfamethoxazole-Trimethoprim
Infections transmises par le sang+19
+ Maladies génito-urinaires
+ Maladies Génitales
Étude thérapeutique
Résumé
Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed. In Part A, patients receive sulfamethoxazole-trimethoprim (SMX/TMP) alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs, each over 2-week periods in a randomly assigned order. Patients in Part B receive the same regimens except with clarithromycin substituted for rifabutin. In Part C, patients receive dapsone alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs in the same manner as in Part A. Part D patients receive the same regimen as those in Part C, except with clarithromycin substituted for rifabutin. Patients are followed every 2 weeks.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.48 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.De 18 à 65 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
Inclusion Criteria Concurrent Medication: Allowed: Antiretroviral therapy provided patient has been on a stable dose for at least 4 weeks prior to study entry. Methadone for drug abuse programs provided patient has been on a stable dose for at least 4 weeks prior to the study. Patients must have: HIV infection. CD4 count >= 200 cells/mm3. No active opportunistic infection. Prior Medication: Allowed: Antiretroviral therapy. Methadone for drug abuse therapy. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Suspicion of gastrointestinal malabsorption problems (at discretion of investigator). Known hypersensitivity to dapsone, SMX, or other sulfonamides, trimethoprim, clarithromycin, rifabutin or other rifamycins, fluconazole, or other azoles. G-6-PD deficiency or methemoglobinemia (in Part C and D patients only). Concurrent Medication: Excluded: Cytolytic agents. Amiodarone. Anesthetics, general. Astemizole. Azithromycin. Barbiturates. Carbamazepine. Cimetidine. Ciprofloxacin. Cisapride. Clarithromycin (except as required on study). Clotrimazole. Dexamethasone. Disulfiram. Erythromycin. Fluoroquinolones. Fluoxetine. Gestodene. Hydrochlorothiazide. Hypoglycemics, oral. Isoniazid. Itraconazole. Ketoconazole. Levomepromazine. Loratadine. MAO inhibitors. Methoxsalen. Miconazole. Nafcillin. Narcotic analgesics. Naringenin. Nifedipine. Norethindrone. Pentazocine. Phenothiazines. Phenytoin. Protease inhibitors. Quinidine. Ranitidine. Rifabutin (except as required on study). Rifampin. Sedative hypnotics. Sulfaphenazole. Terfenadine. Tranquilizers (unless allowed by investigator). Tricyclic and tetracyclic antidepressants. Troleandomycin. Warfarin. Concurrent Treatment: Excluded: Radiation therapy. Prior Medication: Excluded: Cytolytic agents within 5 years prior to study entry. Rifabutin and/or rifampin within 4 weeks prior to study entry. Fluconazoles or other azoles within 4 weeks prior to study entry. Glutathione, glutathione precursors, or related prodrugs within 2 weeks prior to study entry. Excluded within 72 hours prior to study entry: Amiodarone. Anesthetics, general. Astemizole. Azithromycin. Cimetidine. Ciprofloxacin. Cisapride. Clarithromycin. Dexamethasone. Disulfiram. Erythromycin. Fluoroquinolones. Fluoxetine. Hydrochlorothiazide. Hypoglycemics, oral. Isoniazid. Levomepromazine. Loratadine. MAO inhibitors. Methoxsalen. Nafcillin. Narcotic analgesics. Naringenin. Nifedipine. Norethindrone. Pentazocine. Phenothiazines. Phenytoin. Protease inhibitors. Quinidine. Ranitidine. Sedative hypnotics. Sulfaphenazole. Terfenadine. Tranquilizers (unless allowed by investigator). Troleandomycin. Warfarin. Excluded within 4 weeks prior to study entry: Barbiturates. Carbamazepine. Clotrimazole. Gestodene. Itraconazole. Ketoconazole. Miconazole. Omeprazole. Rifabutin. Rifampin. Tricyclic and tetracyclic antidepressants. Prior Treatment: Excluded: Blood transfusion within 1 week prior to study entry. Radiation therapy within 5 years prior to study entry. Active drug or alcohol abuse or dependence that would preclude completion of study.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 2 sites
University of Washington AIDS CRS
Seattle, United States