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
| العنوان: | 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 |
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| المؤلفون: | L. C. K. Wong, B. J. Payne, J. D. Young, L. E. Sendelbach, W. C. Kenney, D. P. Bell, L. Langlois, C. P. Lebel |
| المصدر: | Human & Experimental Toxicology. 14:909-915 |
| بيانات النشر: | SAGE Publications, 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | Male, Interleukin 2, Injections, Subcutaneous, Health, Toxicology and Mutagenesis, Biological Availability, Bone Marrow Cells, Enzyme-Linked Immunosorbent Assay, Pharmacology, Toxicology, Absorption, Rats, Sprague-Dawley, Leukocyte Count, Route of administration, Pharmacokinetics, Bone Marrow, White blood cell, Leukocytes, medicine, Animals, Lung, business.industry, Organ Size, General Medicine, Recombinant Proteins, Rats, Bioavailability, medicine.anatomical_structure, Liver, Pharmacodynamics, Injections, Intravenous, Toxicity, Interleukin-2, Female, Lymph Nodes, Bone marrow, business, Spleen, Half-Life, medicine.drug |
| الوصف: | Comparative pharmacotoxicity studies in rats were per formed to evaluate the response to r-metHuIL-2[ala-125] following 2 or 4 weeks of daily intravenous or sub cutaneous administration, as well as to evaluate pharmacokinetic and pharmacodynamic responses. Pharmacokinetic analysis indicated that r-metHuIL-2[ala- 125] showed high bioavailability and nonlinear concentra tion 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 μg kg-1day-1) indi cated that r-metHuIL-2[ala-125], whether given intra venously or subcutaneously, was associated with increased circulating and infiltrating levels of lympho cytes and eosinophils. Bone marrow lymphoid hyperpla sia and splenic extramedullary hematopoiesis were simi larly 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 histopatholog ic finding described as hepatocyte single cell necrosis which was observed following both intravenous and sub cutaneous administration and was considered to be a toxic response to high doses of r-metHuIL-2[ala-125]. The no observable adverse effect level (NOAEL) for r-metHuIL- 2[ala-125] via intravenous administration was 6 μg kg-1day-1, while that for subcutaneous administration was 30 μg kg-1day-1. Data herein present a form of rHuIL-2 with pharmacokinetic and pharmacodynamic profiles that are similar when given by these two systemic routes. Pharmacotoxic data, based on NOAELs, suggest that sub cutaneous administration may be a preferred clinical route of administration. |
| تدمد: | 1477-0903 0960-3271 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6296f74492c4a1cace9f6a5299a87a48 https://doi.org/10.1177/096032719501401109 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....6296f74492c4a1cace9f6a5299a87a48 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14770903 09603271 |
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