Status:

COMPLETED

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

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Conditions:

Bacterial Infections

Mycoses

Eligibility:

All Genders

18-65 years

Phase:

PHASE1

Brief Summary

To determine the effects of fluconazole and either rifabutin or clarithromycin, alone and in combination, on the pharmacokinetics of first sulfamethoxazole-trimethoprim and then dapsone in HIV-infecte...

Detailed Description

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...

Eligibility 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.

Key Trial Info

Start Date :

Trial Type :

INTERVENTIONAL

End Date :

May 1 1999

Estimated Enrollment :

48 Patients enrolled

Trial Details

Trial ID

NCT00000826

End Date

May 1 1999

Last Update

October 29 2021

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Ucsf Aids Crs

San Francisco, California, United States

2

University of Washington AIDS CRS

Seattle, Washington, United States, 98122