Quantitation of the renal clearance of interleukin-2 using nephrectomized and ureter-ligated rats.
The objective of this work was to determine the role of the kidneys in the systemic clearance rate (CL) of interleukin-2 (IL-2). Rats received IL-2 by i.v. bolus and the pharmacokinetic data were found to be well described by a two-compartment, first-order elimination model. With administration of 0.2, 0.5 or 1.0 mg/kg of IL-2 (n = 3 per treatment), the median alpha and beta half-lives (T1/2 alpha, 2.3 min; T1/2 beta, 13.2 min, respectively), initial volume of distribution (V1, 93 ml/kg), volume of distribution at steady state (Vss, 198 ml/kg) and CL (16.8 ml min-1 kg-1) did not vary with the dose (P = .05). This demonstration of first-order kinetics suggested that renal CL remains constant over a range of doses. The pharmacokinetic properties of 1.0 mg/kg of IL-2 were examined after either single or double nephrectomy (n = 3 and 4, respectively), sham operation (n = 4) or no renal operation (n = 4; the "controls"). No difference in median T1/2 alpha, T1/2 beta, V1, Vss or CL was detected between control and sham-operated rats nor between single nephrectomy and sham operation. Compared with sham operation, double nephrectomy showed no significant change in V1 or Vss but the T1/2 alpha and T1/2 beta approximately doubled and CL was reduced by 75%. In a separate experiment, ureter-ligated rats were compared with sham-operated rats. With ureter ligation, T1/2 alpha, T1/2 beta, V1 and Vss were unchanged but CL was reduced by 36%.
Gibbons
J A
JA
Department of Pharmacology, Pharmacokinetics and Toxicology, Chiron Corporation, Emeryville, California.
Luo
Z P
ZP
Hannon
E R
ER
Braeckman
R A
RA
Young
J D
JD
D000818:Animals; D007376:Interleukin-2 / Q000378:metabolism* / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008297:Male; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D051381:Rats; D014513:Ureter
D007376:Interleukin-2