PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF SUBCUTANEOUSLY ADMINISTERED RECOMBINANT HUMAN INTERLEUKIN-3 FOLLOWING CHEMOTHERAPY FOR NON-HODGKINS-LYMPHOMA

The pharmacokinetics and the pharmacodynamic profile of subcutaneously administered recombinant human non-glycosylated interleukin-3 (rhIL-3 ) was studied in lymphoma patients after standard CHOP chemotherapy. 3 0 patients received 0.5, 1.0, 5.0, 7.5 and 10 mu g/kg (six patients at each dose level) of rhIL-3 for 14d. Serum rhIL-3 samples were obtaine d regularly during the treatment and serially over a 24h period on the first (cycle day 2) and the last (cycle day 15) day of rhIL-3 treatme nt for pharmacokinetic evaluation. Following s.c. injection on cycle d ay 2, the maximum rhIL-3 serum concentration ranged from 289 pg/ml (0. 5 mu g/kg) to 4690 pg/ml (10 mu g/kg). Both the maximum serum concentr ation (R=0.90, P<0.0001) and the area under the serum concentration-ti me curve (R=0.95, P<0.0001) were related to dose. The elimination half -life T-1/2 beta was 160 min for 0.5 mu g/kg and 134 min for 10 mu g/k g, with no apparent dose relationship. The systemic clearance of 3.0-6 .0 ml/min/kg was comparable at all dose levels. No significant differe nce was noted between pharmacokinetic parameters on the first day of r hIL-3 and the last day of treatment, and no accumulation of the drug w as noted throughout the study. The pharmacokinetic parameters correlat ed poorly to the clinical response of the growth factor, where dose in mu g/kg seemed to be the most important single factor.