The Effects of Zidovudine on the Blood of HIV-Infected Patients - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Glaxo Wellcome
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000965

Purpose

To define the pharmacokinetic parameters (blood levels) of total phosphorylated zidovudine (AZT) in peripheral blood mononuclear cells (PBMC) from HIV-infected patients.

Despite an understanding of the serum (or plasma) pharmacokinetics (blood levels) of AZT, a therapeutic concentration range and optimal dosing interval have not yet been determined.

Condition	Intervention
HIV Infections	Drug: Zidovudine

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Pharmacokinetics of Total Phosphorylated Zidovudine in Mononuclear Cells From HIV-Infected Patients

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

20

Detailed Description:

Despite an understanding of the serum (or plasma) pharmacokinetics (blood levels) of AZT, a therapeutic concentration range and optimal dosing interval have not yet been determined.

Three studies are planned on two separate patient groups. Group (1) Patients who have never taken AZT start on a standard dose of AZT. Blood samples are taken hourly for an 8-hour period on days 1 and 14. Other blood samples are taken on days 2, 4, and 8. Group (2) Patients who have never taken AZT are given a standard dose for the first week, increasing each week until week 5. Blood samples are taken at the end of each weekly treatment. After 4 weeks of standard treatment, patients in groups 1 and 2 return and receive a single morning dose of oral AZT. Blood samples are taken immediately before dosing and at 1, 2, 4, 6, and 8 hours after dosing. After a 48-hour clearance period, patients return and resume dosing. Blood samples are again taken over an 8-hour period. After 24 weeks of standard treatment, the pharmacokinetic studies are repeated.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

FDA-approved anti-pneumocystis and antifungal prophylactic or suppressive regimens.
Acyclovir for up to 3 weeks intermittently.

Patients must:

Meet current guidelines for receiving prescription zidovudine.
Have written informed consent from both subject and parent or guardian if under 18. Be capable of understanding and giving informed consent. Women and minorities are actively encouraged to participate.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Malabsorption syndrome (3 or more loose stools/day for at least 4 weeks associated with unintentional weight loss of greater than 10 percent of body weight).

Concurrent Medication:

Excluded:

Probenecid or non-FDA approved investigational drugs.
Systemic chemotherapy.
Other antiviral agents, licensed or investigational, including ganciclovir, foscarnet, ribavirin, didanosine (ddI), dideoxycytidine (ddC), and dideoxydidehydrothymidine (D4T).

Chronic acyclovir.

-

Patients with the following are excluded:

Active bacterial, fungal, or viral infection requiring systemic therapy not specifically allowed.
Significant, chronic medical conditions that could impair compliance with study treatment.

Prior Medication:

Excluded:

Zidovudine (AZT).
Systemic chemotherapy within previous 6 months.
Acyclovir within 30 days of study entry.

Risk Behavior:

Excluded:

Unable to take oral medication reliably.
Alcohol or drug abuse that could impair compliance with study treatment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000965

Locations

United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Glaxo Wellcome

Investigators

Study Chair:	B Stretcher
Study Chair:	P Frame
Study Chair:	A Pesce

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

Publications:

Stretcher BN, Pesce AJ, Frame PT, Greenberg KA, Stein DS. Correlates of zidovudine phosphorylation with markers of HIV disease progression and drug toxicity. AIDS. 1994 Jun;8(6):763-9.

Stretcher BN. Pharmacokinetic optimisation of antiretroviral therapy in patients with HIV infection. Clin Pharmacokinet. 1995 Jul;29(1):46-65. Review.

Stretcher BN, Pesce AJ, Frame PT, Stein DS. Pharmacokinetics of zidovudine phosphorylation in peripheral blood mononuclear cells from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Jul;38(7):1541-7.

Study ID Numbers:	ACTG 161
Study First Received:	November 2, 1999
Last Updated:	August 25, 2008
ClinicalTrials.gov Identifier:	NCT00000965 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Leukocytes, Mononuclear
Drug Evaluation
Acquired Immunodeficiency Syndrome

AIDS-Related Complex
Zidovudine
Phosphorylation

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010