PHARMACOKINETIC BASIS FOR OPTIMAL HEMATOPOIETIC EFFECTIVENESS OF HOMOLOGOUS IL-3 ADMINISTERED TO RHESUS-MONKEYS

To design an interleukin-3 (IL-3) administration schedule for optimal hemopoietic effectiveness, serum half-life (t1/2) was determined after intravenous (i.v) and subcutaneous (s.c.) bolus injections. The initi al t1/2 in serum after i.v. injection was about 10 minutes and the ter minal t1/2 close to 2 hours. Subcutaneous administration resulted in p lateau levels after 2 to 4 hours, while the apparent terminal t1/2 was similar to that after i.v. infusion. The bioavailability of IL-3 foll owing subcutaneous administration was only about 40% of that following i.v. administration. Hemopoietic effects of continuous i.v. infusion of IL-3 was then compared to s.c. administration in either one, two, o r three dally injections. Doses chosen ranged from 1 to 30 mug/kg per day. In agreement with the more limited bioavailability of IL-3 follow ing s.c. administration, continuous i.v. infusion was much more effect ive in stimulating hemopoiesis than s.c. administration. Two or three daily s.c. injections did not improve the hemopoietic response compare d to a single s.c. injection, which is in agreement with the apparent terminal t1/2 of 101 min. It is concluded that IL-3 is more effective by continuous i.v. infusion than by subcutaneous administration.