Development of a new treatment strategy using TDM for next generation anticancer drug

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Akita University
• Principal Investigator: Miura Masatomo 秋田大学, 医学部, 教授 (30265194)
• Co-Investigator(Renkei-kenkyūsha): Takahashi Naoto 秋田大学, 医学部血液腎臓膠原病内科, 教授 (80344753) ; Shibata Hiroyuki 秋田大学, 医学部臨床腫瘍学, 教授 (60393732) ; Tsuchiya Norihiko 秋田大学, 医学部泌尿器科学, 准教授 (70282176)
• Research Collaborator: Kagaya Hideaki 秋田大学, 医学部附属病院薬剤部 ; Abumiya Maiko 秋田大学, 医学部附属病院薬剤部
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 分子標的抗がん剤 / 血中濃度 / 精密医療

Outline of Final Research Achievements

Patients with axitinib C0 more than 5.0 ng/mL showed a tendency toward longer PFS than those with < 5.0 ng/mL. The mean axitinib AUC was significantly higher in patients with the SLCO1B1*15 than without. HPLC-UV method was used to measure the plasma concentrations of regorafenib, active metabolites, M-2 and M-5. Although the therapeutic window of regorafenib cannot yet clarify in the present study, the higher M-5 C0 seems to be related to the side effects of regorafenib. Plasma concentrations of lenalidomide were analyzed by LC-MS/MS. The AUC of lenalidomide can be predicted by the formula using 2 time points, C0h and C4h, in combination with CCr. In Caco-2 cells, the basal-to-apical apparent permeability of lenalidomide was changed, but no change for apical-to-basal, after treatment of the cells with clarithromycin. Clarithromycin inhibited the efflux activity of P-glycoprotein. The lenalidomide C0 was significantly associated with the occurrence of non-hematotoxicity (>21 ng/mL).

Free Research Field

薬物動態学