Pharmacokinetic–Pharmacodynamic Analysis of Sunitinib-Induced Thrombocytopenia in Japanese Patients with Renal Cell Carcinoma

• Nagata Masashi

  Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University

• Ishiwata Yasuyoshi

  Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University

• Takahashi Yutaka

  Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University

• Takahashi Hiromitsu

  Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University

• Saito Kazutaka

  Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

• Fujii Yasuhisa

  Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

• Kihara Kazunori

  Department of Urology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

• Yasuhara Masato

  Department of Pharmacokinetics and Pharmacodynamics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

抄録

The aim of the present study was to clarify the therapeutic range and adequate dose of sunitinib in Japanese renal cell carcinoma patients by means of a pharmacokinetic–pharmacodynamic analysis of sunitinib-induced thrombocytopenia. Six patients with renal cell carcinoma were enrolled in this study. After starting the sunitinib treatment, between three and seven blood samples were obtained from each patient just before the administration of sunitinib. Serum concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were fit to the 1-compartment model with first-order absorption. Changes in platelet counts were fit to the pharmacokinetic–pharmacodynamic model, in which the proliferation of platelet progenitor cells was assumed to be linearly inhibited by sunitinib and its metabolite. All patients using 50 mg as an initial dose of sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic–pharmacodynamic model created successfully described the time course of sunitinib-induced thrombocytopenia and could predict changes in platelet counts after alterations to the dosage of sunitinib administered. The simulation results indicated that the total trough level of sunitinib to avoid severe thrombocytopenia should be <100 ng/mL, and also that the initial daily dose of sunitinib could be reduced to 37.5 mg or 25 mg in most Japanese patients. In addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring of platelet counts is required for the safe use of sunitinib.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (3), 402-410, 2015

  公益社団法人 日本薬学会

キーワード

• sunitinib
• pharmacokinetic–pharmacodynamic analysis
• thrombocytopenia
• renal cell carcinoma

詳細情報

• CRID: 1390282679608050816
• NII論文ID: 130004872283
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00636
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026193221
• PubMed: 25757921
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026193221
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/3/38_b14-00636/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015360251
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可