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Disposition characteristics of recombinant human interleukin-11 after a bolus intravenous administration in mice

A Takagi, H Masuda, Y Takakura and M Hashida

Department of DDS Research, Yamanouchi Pharmaceutical Co., Ltd., Shizuoka, Japan.

The pharmacokinetics and disposition characteristics of recombinant human interleukin-11 (rhIL-11) after systemic administration of 10 to 1000 micrograms/kg was investigated in mice. After a bolus i.v. injection of 100 micrograms/kg of 111In-labeled rhIL-11, radioactivity disappeared rapidly from the circulation after a biexponential function. Plasma clearance profiles based on immunoreactivity and biological activity were identical to the disappearance pattern of radioactivity in the early phase after injection. In the range of 10 to 100 micrograms/kg, pharmacokinetic parameter estimates such as the T1/2 alpha and total body clearance were almost constant, suggesting that pharmacokinetics of rhIL-11 were linear within this dose range. 111In- labeled rhIL-11 distributed mainly to the kidney and liver; within 10 min, 40 and 20% of the dose, respectively, accumulated. On the other hand, the urinary excretion ratio was very small (ca., 1% of the dose), suggesting that rhIL-11 was cleared rapidly by glomeruler filtration followed by efficient tubular reabsorption. Pharmacokinetic analysis of the tissue distribution data demonstrated large kidney and hepatic uptake clearances. At the highest dose (1000 micrograms/kg), total body clearance significantly decreased, due primarily to saturation of hepatic uptake. These findings will provide useful information for the development of rhIL-11.

Volume 275, Issue 2, pp. 537-543, 11/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics.