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Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients

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Summary

We studied the pharmacokinetics of recombinant methionyl human interleukin-2 alanine (r-met-Hu IL-2 [ala 125]) given at high doses by i. v. bolus according to Rosenberg’s initial schedule in seven patients with advanced cancer. Serum concentrations of IL-2 were measured by radio-immunoassay. The drug followed second-order kinetics. During the administration of repeated high doses of IL-2, we noted a progressive increase in the volume of distribution (from 5,984 ± 1,850 to 9,084 ± 4,345 ml) and a progressive decrease in the AUC (from 32,643 ± 3,817 to 22,397 ± 511 IU min ml−1) and β-half-life (from 61 ± 14 to 48 ± 6 min); the peak serum IL-2 concentrations also decreased significantly. We attribute these findings to an expansion of the extracellular fluid space and an increase in the number of IL-2 target cells during the treatment.

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Authors and Affiliations

  1. Service de Médecine Interne et Laboratoire d’Investigation Clinique H. J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de l’Université Libre de Bruxelles, rue Héger-Bordet 1, B-1000, Bruxelles, Belgium

    J. P. Sculier, J. J. Body, N. Donnadieu, S. Nejai, F. Glibert, N. Raymakers & M. Paesmans

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  1. J. P. Sculier
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  2. J. J. Body
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  3. N. Donnadieu
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  4. S. Nejai
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  5. F. Glibert
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  6. N. Raymakers
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  7. M. Paesmans
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Sculier, J.P., Body, J.J., Donnadieu, N. et al. Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients. Cancer Chemother Pharmacol 26, 355–358 (1990). https://doi.org/10.1007/BF02897293

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  • DOI: https://doi.org/10.1007/BF02897293

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