Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients.
We studied the pharmacokinetics of recombinant methionyl human interleukin-2 alanine (r-met-Hu IL-2 [ala 125]) given at high doses by i.v. bolus according to Rosenberg's initial schedule in seven patients with advanced cancer. Serum concentrations of IL-2 were measured by radio-immunoassay. The drug followed second-order kinetics. During the administration of repeated high doses of IL-2, we noted a progressive increase in the volume of distribution (from 5,984 +/- 1,850 to 9,084 +/- 4,345 ml) and a progressive decrease in the AUC (from 32,643 +/- 3,817 to 22,397 +/- 511 IU min ml-1) and beta-half-life (from 61 +/- 14 to 48 +/- 6 min); the peak serum IL-2 concentrations also decreased significantly. We attribute these findings to an expansion of the extracellular fluid space and an increase in the number of IL-2 target cells during the treatment.
Service de Médecine Interne, Institut Jules Bordet, Université, Libre de Bruxelles, Belgium.
J P
JP
Sculier
J J
JJ
Body
N
N
Donnadieu
S
S
Nejai
F
F
Glibert
N
N
Raymakers
M
M
Paesmans
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000628:therapy; D003110:Colonic Neoplasms / Q000097:blood / Q000628:therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000097:blood / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins