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 Fujita, Ken-ichi
A1 Sunakawa, Yu
A1 Miwa, Keisuke
A1 Akiyama, Yuko
A1 Sugiyama, Minako
A1 Kawara, Kaori
A1 Ishida, Hiroo
A1 Yamashita, Keishi
A1 Mizuno, Keiko
A1 Saji, Shigehira
A1 Ichikawa, Wataru
A1 Yamamoto, Wataru
A1 Nagashima, Fumio
A1 Miya, Toshimichi
A1 Narabayashi, Masaru
A1 Ando, Yuichi
A1 Hirose, Takashi
A1 Sasaki, Yasutsuna
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.