title: Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.
abstract: 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.
authors.affiliation: Department of DDS Research, Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ozumi Yaizu, Shizuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Yabe
authors.forename: Y
authors.initials: Y
authors.lastname: Oka
authors.forename: K
authors.initials: K
authors.lastname: Sawai
authors.forename: Y
authors.initials: Y
authors.lastname: Takakura
authors.forename: M
authors.initials: M
authors.lastname: Hashida
mesh_terms: 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
chemical_list: D007205:Indium Radioisotopes; D017370:Interleukin-11; D011994:Recombinant Proteins