RECOMBINANT HUMAN INTERLEUKIN-3 - PHARMACOKINETICS AFTER INTRAVENOUS AND SUBCUTANEOUS BOLUS INJECTION AND EFFECTS ON GRANULOCYTE KINETICS

The pharmacokinetics of E. coli derived recombinant human interleukin- 3 (rhIL-3) was studied following intravenous (i.v.) and subcutaneous ( s.c.) bolus injection of rhIL-3. After i.v. bolus injection in eight p atients, serum peak levels of 34.5-135.0 ng/ml were reached, followed by a rapid decline with a t(1/2)alpha of 17 +/- 2 min and a t(1/2)beta of 59 +/- 7 min. After s.c. bolus injection in five patients, the abs orption was more prolonged with peak serum levels reached at 2.8 +/- 0 .4 h. Elimination was also more protracted, and serum base-line levels were reached at 14-24 h. The immediate effect of rhIL-3 on peripheral white blood cells was less pronounced and more variable than previous ly found for G- or GM-CSF. Following i.v. administration, neutrophils showed a moderate drop to median 64% of initial values (range 42-85%) at median 30 min after injection (range 15-60 min) followed by an incr ease at 24 h to 69-288% of initial values. Eosinophils dropped to a me dian nadir of 34% and then gradually increased to maximum Values in th e range 135-720% at 18-24 h. The effect of rhIL-3 was further examined following i.v. injection of autologous (111)Indium-labelled granulocy tes in six patients. In steady state, i.v. injection of rhIL-3 caused a moderate drop in (111)Indium activity of peripheral blood within 20 min without tendency to subsequent recovery. No change occurred in the activity recorded over the lungs and liver. The activity over the spl een decreased moderately in two patients. These results are strikingly different from those previously obtained after i.v. injection of rhGM -CSF.