PT  - JOURNAL ARTICLE
AU  - Fujita, Ken-ichi
AU  - Sunakawa, Yu
AU  - Miwa, Keisuke
AU  - Akiyama, Yuko
AU  - Sugiyama, Minako
AU  - Kawara, Kaori
AU  - Ishida, Hiroo
AU  - Yamashita, Keishi
AU  - Mizuno, Keiko
AU  - Saji, Shigehira
AU  - Ichikawa, Wataru
AU  - Yamamoto, Wataru
AU  - Nagashima, Fumio
AU  - Miya, Toshimichi
AU  - Narabayashi, Masaru
AU  - Ando, Yuichi
AU  - Hirose, Takashi
AU  - Sasaki, Yasutsuna
TI  - Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure
AID  - 10.1124/dmd.110.035451
DP  - 2011 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 161--164
VI  - 39
IP  - 2
4099  - http://dmd.aspetjournals.org/content/39/2/161.short
4100  - http://dmd.aspetjournals.org/content/39/2/161.full
SO  - Drug Metab Dispos2011 Feb 01; 39
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.