Delayed elimination of SN-38 in cancer patients with severe renal failure.
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.
Fujita
Ken-ichi
K
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
Sunakawa
Yu
Y
Miwa
Keisuke
K
Akiyama
Yuko
Y
Sugiyama
Minako
M
Kawara
Kaori
K
Ishida
Hiroo
H
Yamashita
Keishi
K
Mizuno
Keiko
K
Saji
Shigehira
S
Ichikawa
Wataru
W
Yamamoto
Wataru
W
Nagashima
Fumio
F
Miya
Toshimichi
T
Narabayashi
Masaru
M
Ando
Yuichi
Y
Hirose
Takashi
T
Sasaki
Yasutsuna
Y
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
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D020719:Glucuronides; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme; C441475:7-ethyl-10-hydroxycamptothecin glucuronide