In vivo pharmacokinetic study of exogenously administered recombinant human Interleukin-2 = Recombinant human Interleukin-2의 생체내 약리 역동학적 연구

Abstract

The ability of recombinant human interleukin-2 (rHIL-2) has resulted in its clinical utilization both as a single agent and in combination with lymphokine-activated killer cells. However, its clinical application has been restricted by its dose-related toxicity. In this report, we have studied the serum level of rHIL-2 administered by intraperitoneal (ip), intravenous (iv), or intramuscular (im) route in rats or mice. IL-2 injected ip in rats and mice was absorbed rapidly into circulation to reach peak blood level in 5 minutes, then cleared off quickly with Ti/2 of 30 minutes. IL-2 injected iv seemed to be inactivated or eliminated almost instantly and its TI/2 was only 5 minutes. IL~2 availability in serum after im injection of IL~2 was so variable and low that im injection was not the appropriate way to get enough therapeutic blood concentration. Lethality test showed that 5 父 106 unit/kg of IL--2 given iv or 1.3 x 107 unit/kg given ip was fatal immediately of in 24 hours observation period. Therefore, our study suggests that effective safe way of maintaining serum IL-2 level is via continuous ip injection rather than iv or im.