Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim 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.