PHARMACOKINETICS OF RECOMBINANT HUMAN INTERLEUKIN-2 IN ADVANCED RENAL-CELL CARCINOMA PATIENTS FOLLOWING SUBCUTANEOUS APPLICATION

Aims The aim of the study was to investigate the pharmacokinetics of r ecombinant human interleukin-2 (rhIL-2) in patients with metastatic re nal cell carcinoma following different subcutaneous (s.c.) administrat ion regimens. Methods RhIL-2 was administered subcutaneously to 10 pat ients according to two different dosing regimens: group A received 20 x 10(6) IU m(-2) once daily and group B 10 x 10(6) IU m(-2) twice dail y (every 12 h). Additionally, in all patients the influence of soluble interleukin-2 receptor (sIL-2R) on the pharmacokinetics of rhIL-2 was investigated. Results The mean area under the serum concentration-tim e curve to 24 h (AUC(0,24 h)) was 627 IU ml(-1) h in treatment group A and 1130 IU ml(-1) h (P=0.029) in treatment group B. In both study gr oups C-max and AUC(0,12 h) were not significantly different. Seventy-t wo hours after the beginning of s.c. rhIL-2 therapy the sIL-2R increas ed significantly (P=0.016), and sIL-2R levels over 1200 pmol(-1) seeme d to reduce the AUC. Conclusions In patients with metastatic renal cel l cancer administration of 20 x 10(6) IU m(-2) of rhIL-2 s.c. in two d aily doses (10 x 10(6) IU m(-2) every 12 h) provides better bioavailab ility and is preferable to the single dose administration.