Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites

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.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety