Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
Clarithromycin
+ Rifabutin
+ Sulfamethoxazole-Trimethoprim
Blood-Borne Infections+19
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.48 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
University of Washington AIDS CRS
Seattle, United States