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Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection

  1. Author:
    Piscitelli, S. C.
    Forrest, A.
    Vogel, S.
    Chaitt, D.
    Metcalf, J.
    Stevens, R.
    Baseler, M.
    Davey, R. T.
    Kovacs, J. A.

  2. Author Address

    Piscitelli SC NIAID, Ctr Clin, Dept Pharm, NIH Bldg 10,Room 1N257 Bethesda, MD 20892 USA NIAID, Ctr Clin, Dept Pharm, NIH Bethesda, MD 20892 USA NIAID, Ctr Clin, Dept Crit Care Med, NIH Bethesda, MD 20892 USA SUNY Buffalo, Sch Pharm Amherst, NY USA Sci Applicat Int Corp Frederick, MD USA
    1. Year: 1998
  2. Journal: Clinical Pharmacology & Therapeutics
    1. 64
    2. 5
    3. Pages: 492-498
  4. Type of Article: Article
  1. Abstract:

    A novel model was developed to characterize the time-varying clearance of recombinant interleukin-2 (IL-2), Sixty-eight patients with human immunodeficiency virus infection received 83 cycles of IL-2 either by continuous infusion or by subcutaneous injection for 5 days, IL-2 concentrations after intravenous infusions peaked at 24 hours and then declined by 55% to 78% during the remainder of the infusion. Soluble IL-2 receptors increased greater than 10-fold before gradually returning to baseline. Subcutaneous administration showed a dose-dependent decrease in area under the concentration-time curve (AUC) between days 1 and 5. A model was developed in 9 patients who had IL-2 concentrations and soluble IL-2 receptors determined by ELISA, Concentrations were fitted by an indirect stimulatory pharmacodynamic model, An additional 59 patients with only IL-2 concentrations were fitted to a simplified empiric model. Both models provided an overall r(2) of 0.99 for the plot of observed versus fitted concentrations. The time-dependent increase in IL-2 clearance, likely receptor-mediated, was well described with use of an indirect-effects pharmacokinetic-pharmacodynamic model. [References: 26]

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