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Pharmacokinetics of recombinant human interleukin‐2 in advanced renal cell carcinoma patients following subcutaneous application
Author(s) -
Kirchner G. I.,
Franzke A.,
Buer J.,
Beil W.,
ProbstKepper M.,
Wittke F.,
Övermann K.,
Lassmann S.,
Hoffmann R.,
Kirchner H.,
Ganser A.,
Atzpodien J.
Publication year - 1998
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1998.00036.x
Subject(s) - pharmacokinetics , medicine , cmax , renal cell carcinoma , dosing , pharmacology , area under the curve , bioavailability , urology , gastroenterology
Aims 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 20×10 6 IU m −2 once daily and group B 10×10 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 C max 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 20×10 6 IU m −2 of rhIL‐2 s.c. in two daily doses (10×10 6 IU m −2 every 12 h) provides better bioavailability and is preferable to the single dose administration.