Pharmacokinetic basis for optimal hemopoietic effectiveness of homologous IL-3 administered to rhesus monkeys
van Gils, F.C.; Westerman, Y.; van den Bos, C.; Burger, H.; van Leen, R.W.; Wagemaker, G.
Leukemia 7(10): 1602-1607
1993
ISSN/ISBN: 0887-6924 PMID: 8412321 Document Number: 420285
To design an interleukin-3 (IL-3) administration schedule for optimal hemopoietic effectiveness, serum half-life (t-1/2) was determined after intravenous (i.v.) and subcutaneous (s.c.) bolus injections. The initial t-1/2 in serum after i.v. injection was about 10 minutes and the terminal t-1/2 close to 2 hours. Subcutaneous administration resulted in plateau levels after 2 to 4 hours, while the apparent terminal t-1/2 was similar to that after i.v. infusion. The bioavailability of IL-3 following 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, or three dally injections. Doses chosen ranged from 1 to 30 mu-g/kg per day. In agreement with the more limited bioavailability of IL-3 following s.c. administration, continuous i.v. infusion was much more effective in stimulating hemopoiesis than s.c. administration. Two or three daily s.c. injections did not improve the hemopoietic response compared to a single s.c. injection, which is in agreement with the apparent terminal t-1/2 of 101 min. It is concluded that IL-3 is more effective by continuous i.v. infusion than by subcutaneous administration.