TY - JOUR T1 - Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 161 LP - 164 DO - 10.1124/dmd.110.035451 VL - 39 IS - 2 AU - Ken-ichi Fujita AU - Yu Sunakawa AU - Keisuke Miwa AU - Yuko Akiyama AU - Minako Sugiyama AU - Kaori Kawara AU - Hiroo Ishida AU - Keishi Yamashita AU - Keiko Mizuno AU - Shigehira Saji AU - Wataru Ichikawa AU - Wataru Yamamoto AU - Fumio Nagashima AU - Toshimichi Miya AU - Masaru Narabayashi AU - Yuichi Ando AU - Takashi Hirose AU - Yasutsuna Sasaki Y1 - 2011/02/01 UR - http://dmd.aspetjournals.org/content/39/2/161.abstract N2 - 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. ER -