Pilot Study to Compare the Pharmacokinetics Parameters in Plasma and Intracellular of Raltegravir Administered Once a Day in Adult Patients Infected With HIV
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Raltegravir
Intervention type(s): Drug
Intervention description(s): Raltegravir 800 mg / 24 hours.
Other intervention name(s): N/P
Intervention MeSH terms: Raltegravir Potassium
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Raltegravir; intracellular concentration; plasmatic concentration; HIV; Treatment experienced