Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00995241
Recruitment Status : Completed
First Posted : October 15, 2009
Last Update Posted : September 10, 2010
Information provided by:
Germans Trias i Pujol Hospital

Brief Summary:
The purpose of this study is to compare plasma and intracellular pharmacokinetic parameters of raltegravir 800 mg administered once daily in HIV infected patients.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Raltegravir Phase 4

Detailed Description:

HIV integrase is the enzyme responsible for transferring the DNA encoded by HIV to host chromosomes, a necessary step for the replication of retroviruses. Raltegravir (RAL) is the first integrase inhibitor approved for HIV treatment of patients infected by this virus. RAL has demonstrated a marked antiretroviral activity against HIV strains resistant to other antiretroviral drug families and high virological efficacy in patients pre-treated so as naïve to antiretroviral treatment. In addition, its safety profile is very favourable.

Unlike what happens with other antiretrovirals such as protease inhibitors, there is not a relationship between the virological response to antiretroviral treatment with RAL and the trough concentration of drug in plasma. Similarly, in vitro studies have shown that, after infection of cultured cells, the rate of viral replication measured by p24 antigen production was continuing inhibited even when RAL was washed from the culture medium from the 8 hours after infection, suggesting the possibility of a post-antibiotic effect of the drug. Either way, as in the case of transcriptase inhibitor nucleoside analogues, this lack of correlation between pharmacokinetics and pharmacodynamics of RAL may only be the result of intracellular accumulation of drug in blood lymphocytes peripheral, which in turn could be explained either by setting the RAL to the pre-integration complex or through the saturation of certain cellular transporters responsible for pumping the RAL from the inside out-cell (efflux transporters). Anyway, the result would be a greater RAL intracellular half-life than plasmatic, which would translate into a clinically persistent antiretroviral effect compared with its concentration in plasma.

Based on the above is possible to suggest that the average life of RAL was longer in the peripheral blood lymphocytes than in plasma, and that this intracellular increased half-life could explain the absence of relationship between trough RAL concentration and its virological efficacy, post-antibiotic effect of RAL found in some studies in vitro which, on the other hand, could be relevant to the possible once-daily administration of raltegravir.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV
Study Start Date : November 2009
Actual Primary Completion Date : December 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Raltegravir 800 mg / 24 hours
Raltegravir 800 mg / 24 hours
Drug: Raltegravir
Raltegravir 800 mg / 24 hours.
Other Name: N/P

Primary Outcome Measures :
  1. Plasmatic and intracellular concentration of raltegravir [ Time Frame: 10 days ]

Secondary Outcome Measures :
  1. Clearance, CL/F [ Time Frame: 10 days ]
  2. Volume of distribution, V/F [ Time Frame: 10 days ]
  3. Elimination half-life, t1/2 [ Time Frame: 10 days ]
  4. Area under the plasma concentration-time curve during the dosing interval AUC0-24 [ Time Frame: 10 days ]
  5. Maximum concentration [ Time Frame: 10 days ]
  6. Time to maximum concentration, Tmax [ Time Frame: 10 days ]
  7. Minimum concentration [ Time Frame: 10 days ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age > 18 years.
  2. HIV documented infection.
  3. Stable antiretroviral treatment for at least 4 weeks.
  4. HIV viral load in plasma <50 copies / mL for at least 12 weeks
  5. Voluntary written informed consent.

Exclusion Criteria:

  1. AIDS-defining illness in the previous 4 weeks
  2. Suspicion of inadequate adherence to antiretroviral therapy
  3. In the case of women, pregnant or breastfeeding, or non-use of contraceptives
  4. History or suspicion of failure to cooperate adequately
  5. Concomitant therapy in the two weeks prior to inclusion in the study with atazanavir, tenofovir, NNRTI, rifampicin, inhibitors of proton pump or other drugs with known interactions with raltegravir.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00995241

Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Principal Investigator: Jose Molto, MD,PhD Germans Trias i Pujol Hospital
Principal Investigator: Marta Valle, MD,PhD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Responsible Party: Fundación LLuita contra la SIDA, Fundación Lluita contra la SIDA Identifier: NCT00995241     History of Changes
Other Study ID Numbers: RAL-IC
First Posted: October 15, 2009    Key Record Dates
Last Update Posted: September 10, 2010
Last Verified: September 2010

Keywords provided by Germans Trias i Pujol Hospital:
intracellular concentration
plasmatic concentration
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action