@article {Fujita161, author = {Ken-ichi Fujita and Yu Sunakawa and Keisuke Miwa and Yuko Akiyama and Minako Sugiyama and Kaori Kawara and Hiroo Ishida and Keishi Yamashita and Keiko Mizuno and Shigehira Saji and Wataru Ichikawa and Wataru Yamamoto and Fumio Nagashima and Toshimichi Miya and Masaru Narabayashi and Yuichi Ando and Takashi Hirose and Yasutsuna Sasaki}, title = {Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure}, volume = {39}, number = {2}, pages = {161--164}, year = {2011}, doi = {10.1124/dmd.110.035451}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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/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.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/39/2/161}, eprint = {https://dmd.aspetjournals.org/content/39/2/161.full.pdf}, journal = {Drug Metabolism and Disposition} }