%0 Journal Article %A Ken-ichi Fujita %A Yu Sunakawa %A Keisuke Miwa %A Yuko Akiyama %A Minako Sugiyama %A Kaori Kawara %A Hiroo Ishida %A Keishi Yamashita %A Keiko Mizuno %A Shigehira Saji %A Wataru Ichikawa %A Wataru Yamamoto %A Fumio Nagashima %A Toshimichi Miya %A Masaru Narabayashi %A Yuichi Ando %A Takashi Hirose %A Yasutsuna Sasaki %T Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure %D 2011 %R 10.1124/dmd.110.035451 %J Drug Metabolism and Disposition %P 161-164 %V 39 %N 2 %X This prospective study is designed to examine the effects of severe renal failure on the pharmacokinetics of irinotecan. The pharmacokinetics of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G) in three cancer patients with severe renal failure [creatinine clearance (Ccr) ≤20 ml/min] who were undergoing dialysis and received 100 mg/m2 irinotecan as monotherapy were prospectively compared with those in five cancer patients with normal renal function (Ccr ≥60 ml/min). To ensure that the subjects had similar genetic backgrounds of UDP-glucuronosyltransferase (UGT) 1A1, patients with UGT1A1*1/*1, *1/*6, or *1/*28 were enrolled. The estimated terminal elimination rate constant of SN-38 in patients undergoing dialysis was approximately one tenth of that in patients with normal renal function (P = 0.025). Approximately 50% of SN-38 was dialyzed with a 2.1-m2 dialysis membrane, whereas 27% was dialyzed with a 1.5-m2 membrane. Our results showed that the elimination of SN-38 was significantly delayed in patients with severe renal failure compared with patients with normal renal function. We demonstrated that SN-38 was partly dialyzed. %U https://dmd.aspetjournals.org/content/dmd/39/2/161.full.pdf