Influence of UGT1A1 *6, *27, and *28 Polymorphisms on Nilotinib-induced Hyperbilirubinemia in Japanese Patients with Chronic Myeloid Leukemia
-
- ABUMIYA Maiko
- Department of Pharmacy, Akita University Hospital
-
- TAKAHASHI Naoto
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine
-
- NIIOKA Takenori
- Department of Pharmacy, Akita University Hospital
-
- KAMEOKA Yoshihiro
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine
-
- FUJISHIMA Naohito
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine
-
- TAGAWA Hiroyuki
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine
-
- SAWADA Kenichi
- Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine
-
- MIURA Masatomo
- Department of Pharmacy, Akita University Hospital
書誌事項
- タイトル別名
-
- Influence of <i>UGT1A1</i> *6, *27, and *28 Polymorphisms on Nilotinib-induced Hyperbilirubinemia in Japanese Patients with Chronic Myeloid Leukemia
この論文をさがす
抄録
Nilotinib potently inhibits human uridine diphosphate-glucuronosyltransferase (UGT1A1) activity, causing hyperbilirubinemia. We investigated the influence of UGT1A1 polymorphisms and nilotinib plasma trough concentrations (C0) on nilotinib-induced hyperbilirubinemia in 34 Japanese patients with chronic myeloid leukemia (CML). The proportion of patients with hyperbilirubinemia was significantly higher among patients with the UGT1A1*6/*6 and *6/*28 genotypes (poor metabolizers) than among those with other genotypes (p = 0.004). The median time to elevation of bilirubin levels in UGT1A1 poor metabolizers was 2.0 weeks (hazard ratio, 6.11). The median time to reduction in nilotinib dose in UGT1A1 poor metabolizers was 4.0 weeks (hazard ratio, 7.52; p = 0.002). Consequently, in the maintenance phase 3 months following the initiation of nilotinib therapy, the median daily dose and C0 of nilotinib were 350 mg/day and 372 ng/mL, respectively, in UGT1A1 poor metabolizers, and 600 mg/day and 804 ng/mL, respectively, in the other patients. Patients at increased hyperbilirubinemia risk could be identified by prospective UGT1A1 genotyping prior to nilotinib therapy. To avoid an interruption of CML treatment due to nilotinib-induced hyperbilirubinemia, it may be beneficial to reduce the initial nilotinib dose to 300–400 mg/day for UGT1A1 poor metabolizers.
収録刊行物
-
- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
-
Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 29 (6), 449-454, 2014
日本薬物動態学会
