RT Journal Article SR Electronic T1 Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 161 OP 164 DO 10.1124/dmd.110.035451 VO 39 IS 2 A1 Ken-ichi Fujita A1 Yu Sunakawa A1 Keisuke Miwa A1 Yuko Akiyama A1 Minako Sugiyama A1 Kaori Kawara A1 Hiroo Ishida A1 Keishi Yamashita A1 Keiko Mizuno A1 Shigehira Saji A1 Wataru Ichikawa A1 Wataru Yamamoto A1 Fumio Nagashima A1 Toshimichi Miya A1 Masaru Narabayashi A1 Yuichi Ando A1 Takashi Hirose A1 Yasutsuna Sasaki YR 2011 UL http://dmd.aspetjournals.org/content/39/2/161.abstract AB 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.