Disposition of recombinant human interleukin-10 in subjects with various degrees of renal function.
The pharmacokinetics of intravenously administered recombinant human interleukin-10 (rHuIL-10) were evaluated in 18 subjects with creatinine clearances (Clcr) between 2.7 and 116.7 mL/min/1.73 m2. Serum samples for rHuIL-10 were obtained over a 48-hour period after a single 25 micrograms/kg i.v. bolus infusion. AUC, total body clearance (Clp), and steady-state volume of distribution (Vdss) were derived by compartmental methods. Analysis of serum concentrations showed statistically significant group differences for log-transformed AUC and original scale Clp (p < 0.01). The AUC and effective half-life increased, while the mean Clp of rHuIL-10 decreased as renal function declined. A linear relationship between AUC and Clcr as well as Clp and Clcr demonstrates that the disposition of rHuIL-10 is altered in subjects with renal insufficiency. No serious adverse events were noted.
Andersen
S R
SR
Hennepin County Medical Center, Minneapolis, Minnesota, USA.
Lambrecht
L J
LJ
Swan
S K
SK
Cutler
D L
DL
Radwanski
E
E
Affrime
M B
MB
Garaud
J J
JJ
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003404:Creatinine / Q000652:urine; D003627:Data Interpretation, Statistical; D005334:Fever / Q000139:chemically induced; D005483:Flushing / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D016753:Interleukin-10 / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D016753:Interleukin-10; D003404:Creatinine