Pharmacokinetic basis for optimal hemopoietic 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 initial t1/2 in serum after i.v. injection was about 10 minutes and the terminal t1/2 close to 2 hours. Subcutaneous administration resulted in plateau 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 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 daily injections. Doses chosen ranged from 1 to 30 micrograms/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 t1/2 of 101 min. It is concluded that IL-3 is more effective by continuous i.v. infusion than by subcutaneous administration.
van Gils
F C
FC
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
Westerman
Y
Y
van den Bos
C
C
Burger
H
H
van Leen
R W
RW
Wagemaker
G
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006413:Hematopoietic System / Q000187:drug effects*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007958:Leukocyte Count; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D007377:Interleukin-3; D011994:Recombinant Proteins