title: Delayed elimination of SN-38 in cancer patients with severe renal failure.
abstract: 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/m(2) 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-m(2) dialysis membrane, whereas 27% was dialyzed with a 1.5-m(2) 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.
authors.affiliation: Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan. fujitak@saitama-med.ac.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Yu
authors.initials: Y
authors.lastname: Sunakawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miwa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Minako
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Kaori
authors.initials: K
authors.lastname: Kawara
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ishida
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamamoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Nagashima
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Miya
authors.forename: Masaru
authors.initials: M
authors.lastname: Narabayashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirose
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D020719:Glucuronides / Q000097:blood; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D011446:Prospective Studies; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000628:therapy; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D020719:Glucuronides; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme; C441475:7-ethyl-10-hydroxycamptothecin glucuronide