PMID: 8588953Nov 1, 1995Paper

Pharmacokinetic, pharmacodynamic, and pharmacotoxic profiles of recombinant-methionyl human interleukin-2[alanine-125] (r-metHuIL-2[ala-125]) following intravenous and subcutaneous administration in rats

Human & Experimental Toxicology
C P LeBelL C Wong

Abstract

Comparative pharmacotoxicity studies in rats were performed to evaluate the response to r-metHuIL-2[ala-125] following 2 or 4 weeks of daily intravenous or subcutaneous administration, as well as to evaluate pharmacokinetic and pharmacodynamic responses. Pharmacokinetic analysis indicated that r-metHuIL-2[ala-125] showed high bioavailability and nonlinear concentration profiles. Pharmacodynamic responses to intravenous or subcutaneous dosing with r-metHuIL-2[ala-125], as measured by white blood cell counts, were comparable. Preclinical safety studies (6, 30, and 150 micrograms kg-1 day-1) indicated that r-metHuIL-2[ala-125], whether given intravenously or subcutaneously, was associated with increased circulating and infiltrating levels of lymphocytes and eosinophils. Bone marrow lymphoid hyperplasia and splenic extramedullary hematopoiesis were similarly observed in each study. This pattern of effects was considered an exaggerated pharmacodynamic response to r-metHuIL-2[ala-125]. Of further note was a histopathologic finding described as hepatocyte single cell necrosis which was observed following both intravenous and subcutaneous administration and was considered to be a toxic response to high doses of r-metHuIL-2[ala-125]. Th...Continue Reading

References

Feb 1, 1992·Bio/technology·G KaplanK A Smith
Nov 1, 1992·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·T Vial, J Descotes
Apr 1, 1991·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J P Siegel, R K Puri
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