Pharmacokinetic Evaluation of Changes in Nevirapine AUC Due to Differences in Weight
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      This study would be a prospective cohort study, stratified by weight. Patients who are stable
      on nevirapine for at least 3 months prior to study entry, but no more than 1year will be
      recruited. For 1 week, subjects will take their morning dose of nevirapine in the clinic (and
      be observed taking it), and given their evening dose to take at home. Subjects will need to
      record the date and time they take their evening dose. At the end of the week, the subjects
      will be sequestered at the clinic for blood draws for a 12hr pharmacokinetic sampling. They
      will not be brought back in at 24hrs as they will need to be redosed after 12hrs. They will
      have Liver Function Tests (LFT's) and other labs drawn at study entry, and one month after
      the end of study. Pharmacokinetic levels will be analyzed using standard mathematical models,
      and Area Under the Curve (AUC), Maximum concentration (Cmax), and Minimum Concentration
      (Cmin) will be compared between groups.
    

Detailed description: 
      This will be a non-randomized, cohort study. 8 patients in each of 3 weight ranges (< 160lb,
      161-200lb, > 200lb) will be recruited to participate in the study. Subjects will be HIV +
      patients currently on stable therapy with nevirapine (on medication for at least 3 months
      with minimal self-reported adherence) as part of a combination regimen for their Human
      Immunodeficiency Virus (HIV) infection (as prescribed by their primary care provider).
      Subjects are to be in good health with liver function tests will be < 2 times normal limits,
      measured within 1 month prior to the study period. All subjects will be male. The reasoning
      for this gender bias is as follows: if both genders are to be used, there should be an equal
      number of male and female subjects to remove any bias from the data. Since there are not
      enough females taking nevirapine to be able to appropriately recruit, females will be
      excluded.

      Subjects will be asked to take their medications the night before the study period between
      8:00pm and 8:30pm, and asked to abstain from alcohol for the 7 days prior to the study. On
      the study day, they will report to the Jeffrey Goodman Special Care Clinic at 7:30, prior to
      breakfast.

      Subjects will randomly be divided into 4 groups during the study period. Four healthcare
      professionals (one physician, one family nurse practitioner, one registered nurse and one
      licensed vocational nurse, will be present throughout the study for catheter insertions and
      blood draws. IV catheters will be inserted upon arrival, with four patients (one from each
      group) having a time zero and receiving their study medication at each time point of 8:00,
      8:05, 8:10, 8:15, 8:20, 8:25 (this is to allow for appropriate work-flow during the blood
      draw portion of the study. Serial blood samples will be drawn after dosing at the following
      times: 0.5hr, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr. Subjects will be allowed to eat breakfast
      (supplied by the study personnel) After the 1hr blood sample. Lunch and dinner will also be
      available for study subjects. 12hr sample, the catheters will be removed and the subjects
      allowed to leave (subjects will not be allowed to leave the premises with the catheter in
      place). Subjects will be paid $250 for their participation after the conclusion of the study.

      Consolidated Laboratory Services will analyze all blood samples for nevirapine levels. AUC's
      and AUC comparisons will be calculated with appropriate statistical software (Systat).

      Pharmacokinetic (PK) Levels:

      Levels will be drawn prior to dosing, and at the following time intervals: 0.5hr, 1hr, 1.5hr,
      2hr, 4hr, 6hr, 8hr, 12hr. ~10cc of blood will be drawn with each sample, centrifuged, and
      plasma separated into 2 cryovials. Samples will then be frozen at -20oC. All samples (216)
      will be sent to Consolidated Laboratory Services for level determination by appropriate
      means.

      Safety monitoring:

      A licensed physician and a licensed family nurse practitioner will be on site for the entire
      study. All study personnel are certified in Basic Life Support (and some in Advanced Cardiac
      Life Support). The clinic facilities are equipped for minor emergencies and 911 will be
      utilized for major emergencies.

      Statistics:

      AUC's will be calculated using non-linear mathematical modeling with statistical software.
      AUC's will be compared using appropriate statistical tests.

      Evaluation of Adverse Events:

      All adverse events will be recorded and treated (if necessary) on site. Adverse events not
      able to be treated on site will be referred to an emergency room or to their primary provider
      the following day (if it is not urgent).
    

Intervention name(s): Nevirapine
Intervention type(s): Drug
Intervention description(s): 200mg twice daily of nevirapine
Intervention MeSH terms: Nevirapine
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        HIV positive patients stable on a nevirapine containing regimen for at least 3 months
      
Biospecimen description: 
      Levels were drawn prior to dosing, and at the following time intervals: 0.5hr, 1hr, 1.5hr,
      2hr, 4hr, 6hr, 8hr, 12hr. ~10cc of blood were drawn with each sample, centrifuged, and plasma
      separated into 2 cryovials. Samples were then frozen at -20oC. All samples (216) weresent to
      Consolidated Laboratory Services for level determination by appropriate means. All samples
      have now been destroyed.
    
Keywords: nevirapine; pharmacokinetics