- 英名：Sunitinib Malate
- 商品名：スーテントカプセル（ファイザー株式会社）
薬物動態パラメータ 
| F | Ae | fub | CLtot | Vd | B/P ratio | CL/F | Vd/F |
| (%) | (%) | (mL/min/kg) | (L/kg) | ||||
| 0.05 |
薬物動態的特徴
- 消失臓器：
- CL：
- Vd：
- タンパク結合：binding sensitive
吸収
食事の影響
- 食事の影響はみられなかった（添付文書より）
性差
分布
- スニチニブ及びN-脱エチル体（100ng/mL〜4000ng/ｍL）のヒト血漿蛋白結合率はそれぞれ約95％及び90％（添付文書）（CTD2.7.2.21.2 p.36）
- 赤血球中濃度/血漿中濃度は約1.4（CTD 2.7.2.2.1.3）
代謝
- 主にCYP3A4によってN-脱エチル体に代謝（添付文書）
- 日本人消化管間質腫瘍患者に本剤25mg及び50mgを反復投与したとき、N-脱エチル体のAUC0-24値はスニチニブの48.5％（添付文書）
排泄
- 未変化体の排泄を検討していない
- ［14C］-標識スニチニブ50mgを単回経口投与したとき、投与後21日目までに投与放射能の61％が糞中、16％が尿中に排泄された（添付文書より）
母集団薬物動態（PPK）解析
腎障害のある患者
- 単回投与しスニチニブ及びN-脱エチル体のCmax及びAUC0-∞を健康被験者（8例、クレアチニンクリアランス＞80mL/min）と比較（添付文書より）
- 重度腎機能障害（クレアチニンクリアランス＜30mL/min）（外国人各8例）：は健康被験者とほぼ同様
- 血液透析を要する末期腎不全被験者（外国人各8例）：健康被験者と比べ、スニチニブのCmax及びAUC0-∞はそれぞれ38％及び47％低下、N-脱エチル体はそれぞれ30％及び31％低下
- 血液透析によりスニチニブ及びN-脱エチル体が除去されることはほとんどなかった
肝機能障害のある患者
- 軽度及び中等度（Child-Pugh分類A及びB）の肝機能障害：健康被験者とほぼ同等（添付文書より）
- 重度（Child-Pugh分類C）の肝機能障害：臨床試験 未（添付文書より）
PK-PD
参考
論文
2003年
- Clin Cancer Res. 2003 Nov 15;9(15):5465-76.
- An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients.
- PMID: 14654525 https://www.ncbi.nlm.nih.gov/pubmed/14654525
2005年
- Blood. 2005 Feb 1;105(3):986-93. Epub 2004 Sep 30.
- A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease.
- PMID: 15459012 https://www.ncbi.nlm.nih.gov/pubmed/15459012
2006年
- J Clin Oncol. 2006 Jan 1;24(1):25-35. Epub 2005 Nov 28.
- Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer.
- PMID: 16314617 https://www.ncbi.nlm.nih.gov/pubmed/16314617
- Anticancer Drugs. 2006 Mar;17(3):353-8.
- Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects.
- PMID: 16520665 https://www.ncbi.nlm.nih.gov/pubmed/16520665
2008年
- Cancer Chemother Pharmacol. 2008 Mar;61(3):515-24. Epub 2007 May 16.
- A phase I and pharmacokinetic study of sunitinib administered daily for 2 weeks, followed by a 1-week off period.
- PMID: 17505827 https://www.ncbi.nlm.nih.gov/pubmed/17505827
2009年
- Clin Cancer Res. 2009 Apr 1;15(7):2497-506. doi: 10.1158/1078-0432.CCR-08-1893. Epub 2009 Mar 3.
- A population pharmacokinetic meta-analysis of sunitinib malate (SU11248) and its primary metabolite (SU12662) in healthy volunteers and oncology patients.
- PMID: 19258444 https://www.ncbi.nlm.nih.gov/pubmed/19258444
- Ann Oncol. 2009 Mar;20(3):599-600. doi: 10.1093/annonc/mdn779. Epub 2009 Jan 19.
- Pharmacokinetics of sunitinib in an obese patient with a GIST.
- PMID: 19153120 https://www.ncbi.nlm.nih.gov/pubmed/19153120
- Ann Oncol. 2009 Jan;20(1):190-2. doi: 10.1093/annonc/mdn626. Epub 2008 Sep 18.
- Pharmacokinetics of sunitinib in hemodialysis.
- PMID: 18801884 https://www.ncbi.nlm.nih.gov/pubmed/18801884
- J Clin Pharmacol. 2010 Apr;50(4):472-81. doi: 10.1177/0091270009347868. Epub 2009 Sep 24.
- Pharmacokinetics and safety of sunitinib malate in subjects with impaired renal function.
- PMID: 19779038 https://www.ncbi.nlm.nih.gov/pubmed/19779038
2010年
- Cancer Chemother Pharmacol. 2010 Jul;66(2):357-71. doi: 10.1007/s00280-009-1170-y. Epub 2009 Dec 5.
- Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis.
- PMID: 19967539 https://www.ncbi.nlm.nih.gov/pubmed/19967539
- Invest New Drugs. 2010 Dec;28(6):866-75. doi: 10.1007/s10637-009-9306-9.
- Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate.
- PMID: 19730791 https://www.ncbi.nlm.nih.gov/pubmed/19730791
- Clin Pharmacol Ther. 2010 May;87(5):601-8. doi: 10.1038/clpt.2010.20. Epub 2010 Apr 7.
- Pharmacokinetic/pharmacodynamic modeling of biomarker response to sunitinib in healthy volunteers.
- PMID: 20376000 https://www.ncbi.nlm.nih.gov/pubmed/20376000
- Cancer Chemother Pharmacol. 2010 Sep;66(4):699-707. doi: 10.1007/s00280-009-1213-4. Epub 2010 Jan 5.
- Pharmacokinetics of sunitinib malate in subjects with hepatic impairment.
- PMID: 20049443 https://www.ncbi.nlm.nih.gov/pubmed/20049443
2011年
- Cancer Sci. 2011 Nov;102(11):1949-57. doi: 10.1111/j.1349-7006.2011.02054.x. Epub 2011 Sep 14.
- Biomarkers to predict response to sunitinib therapy and prognosis in metastatic renal cell cancer.
- PMID: 21812860 https://www.ncbi.nlm.nih.gov/pubmed/21812860
2012年
- Breast. 2012 Aug;21(4):507-13. doi: 10.1016/j.breast.2012.01.012. Epub 2012 Feb 14.
- Clinical and pharmacokinetic study of sunitinib and docetaxel in women with advanced breast cancer.
- PMID: 22336056 https://www.ncbi.nlm.nih.gov/pubmed/22336056
- Drug Metab Pharmacokinet. 2012;27(6):631-9. Epub 2012 Jun 5.
- Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics.
- PMID: 22673043 https://www.ncbi.nlm.nih.gov/pubmed/22673043
2013
- Expert Opin Drug Metab Toxicol. 2013 Jun;9(6):777-88. doi: 10.1517/17425255.2013.791281. Epub 2013 Apr 16.
- Pharmacokinetics and pharmacodynamics of sunitinib for the treatment of advanced pancreatic neuroendocrine tumors.
- PMID: 23590356 https://www.ncbi.nlm.nih.gov/pubmed/23590356
2014
- Br J Cancer. 2014 May 13;110(10):2441-9. doi: 10.1038/bjc.2014.194. Epub 2014 Apr 15.
- Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours.
- PMID: 24736581 https://www.ncbi.nlm.nih.gov/pubmed/24736581
- Anticancer Res. 2014 May;34(5):2283-9.
- Contribution of plasma proteins, albumin and alpha 1-acid glycoprotein, to pharmacokinetics of a multi-targeted receptor tyrosine kinase inhibitor, sunitinib, in analbuminemic rats.
- PMID: 24778032 https://www.ncbi.nlm.nih.gov/pubmed/24778032
- Cancer. 2014 Apr 15;120(8):1194-202. doi: 10.1002/cncr.28554. Epub 2014 Jan 28.
- A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus-positive patients with cancer: AIDS Malignancy Consortium trial AMC 061.
- PMID: 24474568 https://www.ncbi.nlm.nih.gov/pubmed/24474568
コメントをかく