caa a22 4500 477125565 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012063602856 doi (NATIONALLICENCE)springer-10.1023/A:1012063602856 Renal Disposition of Recombinant Human Interleukin-11 in the Isolated Perfused Rat Kidney [Elektronische Daten] [Akira Takagi, Yoshiyuki Yabe, Yoshikazu Oka, Kenzo Sawai, Yoshinobu Takakura, Mitsuru Hashida] Purpose. To clarify the mechanism of the renal clearance of recombinant human interleukin-11 (rhIL-11), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. Methods. The disposition characteristics of 111In-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 (V d ) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 μg/kidney was between 0.35 and 0.40 ml/g kidney. However, V d 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. Plenum Publishing Corporation, 1997 rhIL-11 nationallicence rat kidney perfusion nationallicence glomerular and post-glomerular permselectivity nationallicence tubular reabsorption nationallicence Takagi Akira Department of DOS Research, Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, 180 Ozumi Yaizu, 425, Shizuoka, Japan aut Yabe Yoshiyuki Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut Oka Yoshikazu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut Sawai Kenzo Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut Takakura Yoshinobu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut Hashida Mitsuru Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 86-90 0724-8741 14:1<86 1997 14 11095 https://doi.org/10.1023/A:1012063602856 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012063602856 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takagi Akira Department of DOS Research, Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, 180 Ozumi Yaizu, 425, Shizuoka, Japan aut NATIONALLICENCE 700 1- Yabe Yoshiyuki Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Oka Yoshikazu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Sawai Kenzo Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Takakura Yoshinobu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Hashida Mitsuru Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 86-90 0724-8741 14:1<86 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer