PHARMACOKINETICS OF RECOMBINANT HUMAN INTERLEUKIN-3 IN RHESUS-MONKEYS

Concentration-time profiles of I-125-labeled recombinant human interle ukin-3 ((125)IrhIL-3) were determined by reverse phase high performanc e liquid chromatography (RHPLC) after intravenous and subcutaneous adm inistration of the drug in 16 rhesus monkeys. The initial and terminal T-1/2 in plasma after intravenous of 30 mu g/kg were (0.15 +/- 0.13) and (2.21 +/- 0.59) h, respectively. Terminal half-lives after 30, 90 and 180 mu g/kg subcutaneous (s.c.) injections were 2.0-3.8 h. Area un der concentration-time curves (AUC) following s.c. were roughly increa sed with dose, while CLs were similar among different dosages, The abs orption rates were dependent on concentration at injected site. Bioava ilability was about 0.7 alter s.c. Rapid biodegradation was found in p lasma. Distribution profiles of total radioactivity were as follows: t he highest level was found in urinary system; levels in bile-enteric s ystem, lymph nodes, bone marrow and spleen were near to that in plasma , and level in brain was the lowest. The RHPLC analysis revealed that kidney was one ai the major organs for biodegradation.