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| Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00001001 |
Purpose
To examine the pharmacokinetics (blood levels) and bioavailability of zidovudine (AZT) given to patients with HIV infection and chronic liver disease. The specific aim of the study is to provide data permitting the development of guidelines for use of AZT in patients with mild, moderate, or severe liver disease.
AZT is the only antiviral agent that has been shown to be effective in patients with severe HIV infection. However, AZT is largely eliminated from the body through a biochemical reaction that takes place in the liver, and it is possible that patients with underlying liver disease may have altered AZT pharmacokinetics and may metabolize AZT differently, with the result that they are susceptible to an increased risk of serious drug toxicity. This study will examine the pharmacokinetics, elimination, and metabolism of AZT in patients with liver disease. Guidelines developed from the data will be helpful in managing AZT treatment of these HIV-infected persons and will indicate whether the dose of AZT administered should be adjusted to compensate for any changes in its bioavailability and/or pharmacokinetics.
| Condition | Intervention |
|---|---|
|
HIV Infections Liver Diseases |
Drug: Zidovudine |
| Study Type: | Interventional |
| Study Design: | Treatment, Open Label, Pharmacokinetics Study |
| Official Title: | A Clinical Study Examining the Pharmacokinetics and Bioavailability of Azidothymidine (AZT, Zidovudine) in Patients With Human Immunodeficiency Virus (HIV) Infection and Hepatic Disease |
| Estimated Enrollment: | 39 |
AZT is the only antiviral agent that has been shown to be effective in patients with severe HIV infection. However, AZT is largely eliminated from the body through a biochemical reaction that takes place in the liver, and it is possible that patients with underlying liver disease may have altered AZT pharmacokinetics and may metabolize AZT differently, with the result that they are susceptible to an increased risk of serious drug toxicity. This study will examine the pharmacokinetics, elimination, and metabolism of AZT in patients with liver disease. Guidelines developed from the data will be helpful in managing AZT treatment of these HIV-infected persons and will indicate whether the dose of AZT administered should be adjusted to compensate for any changes in its bioavailability and/or pharmacokinetics.
Patients are assessed and stratified according to liver function and severity of liver disease. Patients receive an intravenous (IV) dose of AZT on the first day of the study, followed by an oral dose 24 hours later on the second day of the study. Patients fast for 8 hours prior to each dose and for 2 hours after each dose. Liver function tests are repeated on the first day of the study. In each patient, serial measurements of serum and urine AZT and its metabolite, 3'-azido-3'-deoxy-5'-glucuronylthymidine (GAZT), are monitored after both doses.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed after completion of day 2 of study:
Concurrent Treatment:
Allowed after completion of day 2 of study:
The study will be divided into three groups of cooperative patients according to mild, moderate, or severe liver disease. Severity of disease will be assessed within 7 days of entry into the study according to laboratory values. Patients must have normal kidney function. No medications should be taken for 48 hours prior to entering the study. Hemophiliacs are included.
Prior Medication:
Allowed:
Exclusion Criteria
Co-existing Condition:
Patients will be excluded from the study if unacceptable toxicity develops or if an illness requiring concurrent treatment develops.
Concurrent Medication:
Excluded within 48 hours of study entry:
Concurrent Treatment:
Excluded within 48 hours of study entry:
Patients will be excluded for the following reasons:
Prior Medication:
Excluded within 48 hours of study entry:
Prior Treatment:
Excluded within 30 days of study entry:
Active drug or alcohol abuse.
Contacts and Locations| United States, Massachusetts | |
| Boston Med Ctr | |
| Boston, Massachusetts, United States, 02118 | |
| Univ of Massachusetts Med Ctr | |
| Worcester, Massachusetts, United States, 01655 | |
| United States, North Carolina | |
| Univ of North Carolina | |
| Chapel Hill, North Carolina, United States, 275997215 | |
| United States, Pennsylvania | |
| Milton S Hershey Med Ctr | |
| Hershey, Pennsylvania, United States, 170330850 | |
| United States, Washington | |
| Univ of Washington | |
| Seattle, Washington, United States, 98105 | |
| Study Chair: | Lemon SM |
More Information
| Study ID Numbers: | ACTG 062 |
| Study First Received: | November 2, 1999 |
| Last Updated: | July 11, 2008 |
| ClinicalTrials.gov Identifier: | NCT00001001 |
| Health Authority: | United States: Federal Government |
|
Liver Liver Diseases Liver Function Tests HIV Seropositivity |
Acquired Immunodeficiency Syndrome Zidovudine Biological Availability |
|
Virus Diseases Sexually Transmitted Diseases, Viral Liver Diseases Digestive System Diseases HIV Seropositivity HIV Infections |
Sexually Transmitted Diseases Acquired Immunodeficiency Syndrome Zidovudine Retroviridae Infections Immunologic Deficiency Syndromes |
|
Antimetabolites Anti-Infective Agents Communicable Diseases RNA Virus Infections Anti-HIV Agents Slow Virus Diseases Immune System Diseases Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |
Infection Antiviral Agents Pharmacologic Actions Reverse Transcriptase Inhibitors Anti-Retroviral Agents Therapeutic Uses Lentivirus Infections Nucleic Acid Synthesis Inhibitors |
