Pharmacokinetics of recombinant human interleukin-2 in advanced renal cell carcinoma patients following subcutaneous application

Br J Clin Pharmacol. 1998 Jul;46(1):5-10. doi: 10.1046/j.1365-2125.1998.00036.x.

Abstract

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 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.

MeSH terms

  • Aged
  • Biological Availability
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy*
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacokinetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics

Substances

  • Interleukin-2
  • Recombinant Proteins