Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.
OBJECTIVE
To clarify the mechanism of the renal clearance of recombinant human interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney.


METHODS
The disposition characteristics of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions.


RESULTS
Steady-state distribution volume (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine.


CONCLUSIONS
The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.
Takagi
A
A
Department of DDS Research, Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ozumi Yaizu, Shizuoka, Japan.
Yabe
Y
Y
Oka
Y
Y
Sawai
K
K
Takakura
Y
Y
Hashida
M
M
D000818:Animals; D006801:Humans; D007205:Indium Radioisotopes; D017370:Interleukin-11 / Q000493:pharmacokinetics* / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000652:urine; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D017370:Interleukin-11; D011994:Recombinant Proteins