ＫＲＮ５７０２の体内動態：　ラットにおけるＫＲＮ５７０２単回皮下投与後の吸収，分布，代謝および排せつ

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  • Metabolic fate of KRN5702: Plasma level, distribution, metabolism and excretion of KRN5702 after a single subcutaneous administration to rats.

抄録

The plasma levels, tissue distribution, metabolism and excretion of KRN5702 after a single subcutaneous administration were investigated in the rats using 125I-KRN5702 and/or a double-antibody radioimmunoassay (RIA) and in vivo bioassay.<BR> After subcutaneous administration of KRN5702 at a dose of 200IU/kg in male rats, the plasma concentration reached the maximum concentration (Cmax) during 8 to 12 hours, and then declined slowly. Cmax after subcutaneous administration was below 10% of the concentration observed at 10 minutes after intravenous administration of the same dose. However, in the elimination phase, the plasma concentration after subcutaneous administration maintained to be relatively higher than that after intravenous administration. The profiles of biological activity in sera, determined by exhypoxic polycythemic mouse bioassay, was almost same as compared with those determined by RIA, and also same as immunoreatcive radioactivity of 125I-KRN5702.<BR> Dose-dependent increase was observed in Cmax, but not observed in half-lives. The half-life and mean residence time (MRT) obtained from subcutaneous administration had been longer when compared with intravenous administration. The bioavailability after subcutaneous administration as estimated by the area under the plasma concentration vs time curve(AUC) accounted for 35.5-54% of the value obtained from intravenous injection. There was no difference in AUC, half-life and other pharmacokinetic parameters between make and female rats.<BR> The majority of tissues both in male and female rats showed a maximum level of radioactivity at 8 hours after administration of 125I-KRN5702, and then decreased in parallel with plasma level in any time interval. High level of radioactivity same as in plasma, were observed in bone marrow, kidney, thyroid and in bladder. Radioactivity in most of other tissues was lower than that in plasma. These results were in good agreement with those of whole body autoradiography. Same distribution profiles of radioactivity were also observed in female rats with the exception of genital organs.<BR> Within 168 hours after subcutaneous administration, most of the administered radioactivity was excreted in urine in the form of free iodine.<BR> These results suggest that KRN5702 adm inistered subcutaneously are slowly transferred into general circulation without degradation at the site of injection. We considered that subcutaneous administration might be advantageous route, since it provides a possibility to maintain the effective plasma concentration of KRN5702.

収録刊行物

  • 薬物動態

    薬物動態 8 (5), 1065-1083, 1993

    日本薬物動態学会

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