Clinical trial NCT00000661: The Pharmacokinetics of Zidovudine and Oxazepam Alone and in Combination in the HIV-Infected Patient
Official title: The Pharmacokinetics of Zidovudine and Oxazepam Alone and in Combination in the HIV-Infected Patient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Oxazepam
Drug Evaluation
Drug Interactions
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To determine if a pharmacokinetic (blood level) interaction exists between zidovudine (AZT) and oxazepam in the HIV-infected patient. Benzodiazepines (such as oxazepam) are among the most frequently prescribed class of drugs and are commonly used therapeutically for patients with chronic disease. This study is important because of the potential for toxicity resulting from a reaction between AZT and benzodiazepines and the likelihood of frequent use of the combination of these drugs in patients with HIV infection.

Detailed description: Benzodiazepines (such as oxazepam) are among the most frequently prescribed class of drugs and are commonly used therapeutically for patients with chronic disease. This study is important because of the potential for toxicity resulting from a reaction between AZT and benzodiazepines and the likelihood of frequent use of the combination of these drugs in patients with HIV infection.

Patients are studied to determine oral and intravenous AZT and single oral dose oxazepam pharmacokinetics. Patients then take AZT and oxazepam together to determine if interactions between the drugs occur.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Required:

* Stable prescribed dosage of zidovudine (AZT), = or \> 500 mg/day.

Allowed:

* Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine.
* Erythropoietin.

Patients must be:

* HIV positive by ELISA and Western blot.
* Currently taking a stable prescribed dosage of 500 mg/day of zidovudine (AZT).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

* Allergy to benzodiazepines or a previously documented intolerance to zidovudine (AZT) therapy of = or \< 600 mg/day.
* Significant underlying medical condition that could impair continuous participation in study.
* Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight).

Concurrent Medication:

Excluded:

* Oral contraceptives.
* Cytotoxic chemotherapy.
* Ganciclovir.
* Flucytosine.
* Probenecid.
* Opiates.
* Valproic acid.
* Sulfa drugs.
* Sucralfate.
* Dapsone.
* Rifampin.
* Antacids within 2 hours of zidovudine (AZT) dose.
* Isoniazid.
* Ketoconazole.
* Pyrimethamine.
* Clindamycin.
* Aspirin.
* Ibuprofen.
* Investigational drugs not specifically allowed.

Patients with the following are excluded:

* Allergy to benzodiazepines or a previously documented intolerance to zidovudine (AZT) therapy of = or \< 600 mg/day.
* Significant underlying medical condition that could impair continuous participation in study.
* Unable to take oral medication reliably.

Prior Medication:

Excluded within 30 days of study entry:

* Antiretroviral agents other than zidovudine (AZT).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Palo Alto Veterans Adm Med Ctr / Stanford Univ
state: California
Study officials:
name: Israelski D
role: STUDY_CHAIR
name: Blaschke T
role: STUDY_CHAIR
References:
citation: Mole LA, Israelski DM, Bubp JL, O'Hanley P, Merigan T, Blaschke T. The pharmacokinetics (PK) of zidovudine (ZDV) and oxazepam (OXA) alone and in combination in the HIV-infected patient (ACTG 124). Int Conf AIDS. 1992 Jul 19-24;8(2):B186 (abstract no PoB 3595)
citation: Mole L, Israelski D, Bubp J, O'Hanley P, Merigan T, Blaschke T. Pharmacokinetics of zidovudine alone and in combination with oxazepam in the HIV infected patient. J Acquir Immune Defic Syndr (1988). 1993 Jan;6(1):56-60.