Pharmacokinetics of recombinant human interleukin-2 in advanced renal cell carcinoma patients following subcutaneous application.
OBJECTIVE
The aim of the study was to investigate the pharmacokinetics of recombinant human interleukin-2 (rhIL-2) in patients with metastatic renal cell carcinoma following different subcutaneous (s.c.) administration regimens.


METHODS
RhIL-2 was administered subcutaneously to 10 patients 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 daily (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-time 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 groups Cmax and AUC(0,12 h) were not significantly different. Seventy-two hours after the beginning of s.c. rhIL-2 therapy the sIL-2R increased significantly (P=0.016), and sIL-2R levels over 1200 pmol l(-1) seemed to reduce the AUC.


CONCLUSIONS
In patients with metastatic renal cell cancer administration of 20 x 10(6) IU m(-2) of rhIL-2 s.c. in two daily doses (10 x 10(6) IU m(-2) every 12 h) provides better bioavailability and is preferable to the single dose administration.
Institute for General Pharmacology, Medizinische Hochschule Hannover, Germany.
G I
GI
Kirchner
A
A
Franzke
J
J
Buer
W
W
Beil
M
M
Probst-Kepper
F
F
Wittke
K
K
Overmann
S
S
Lassmann
R
R
Hoffmann
H
H
Kirchner
A
A
Ganser
J
J
Atzpodien
D000368:Aged; D001682:Biological Availability; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D007376:Interleukin-2; D011994:Recombinant Proteins