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) | ||||
| 98 | 5 | 0.05 | 3.3 | 6.2 |
- 臨床薬物動態学より
薬物動態的特徴
- 消失臓器：肝代謝型
- CL：肝固有クリアランス依存
- Vd：大
- タンパク結合：binding sensitive
吸収
- 静脈内及び経口投与のAUC比より推定したBAは平均98.3％（海外において、健常成人12名を対象とした0108試験、審査報告書＜ヒトにおける薬物動態＞p.24-25）
食事の影響
- 食事摂取に伴う胃内容物排出速度の低下によりtmaxの1.5時間の遅延及びCmaxの15％の低下が認められたが、AUCとしては7％の低下であり臨床的に問題となる影響はない（0109及び0110試験、審査報告書＜ヒトにおける薬物動態＞p.25）
分布
- ヒトにおいて分布容積が435Lと大きい（審査報告書＜ヒトにおける薬物動態＞p.26）
- ヒト血漿蛋白との結合率が約95％（審査報告書＜ヒトにおける薬物動態＞p.26）
- 精製したα1-酸性糖蛋白におけるイマチニブの蛋白結合率を測定した試験において、1.2µg/mLを超える薬物濃度で結合の飽和（審査報告書＜ヒトにおける薬物動態＞p.26）
代謝
- 静脈内投与後のデータから推定された血漿クリアランスは14L/h（海外において、健常成人12名を対象とした0108試験、審査報告書＜ヒトにおける薬物動態＞p.24-25）
排泄
- 尿中へは投与放射能量の13％が排泄され、このうち約5％が未変化体（0107試験、審査報告書＜ヒトにおける薬物動態＞p.25）
母集団薬物動態（PPK）解析
- Br J Clin Pharmacol. 2005 Jul; 60(1): 35–44.
- Table.4
参考
- 承認審査報告書：JAPICデータベース参照（http://www.shinsahoukokusho.jp/）
論文
2003年
- Clin Cancer Res. 2003 Feb;9(2):625-32.
- Alpha1 acid glycoprotein binds to imatinib (STI571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients.
- PMID: 12576428 https://www.ncbi.nlm.nih.gov/pubmed/12576428
2004年
- Cancer Chemother Pharmacol. 2004 Feb;53(2):102-6. Epub 2003 Nov 7.
- Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects.
- PMID: 14605865 https://www.ncbi.nlm.nih.gov/pubmed/14605865
- J Clin Pharmacol. 2004 Feb;44(2):158-62.
- Absolute bioavailability of imatinib (Glivec) orally versus intravenous infusion.
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- J Clin Oncol. 2004 Mar 1;22(5):935-42.
- Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients.
- PMID: 14990650 https://www.ncbi.nlm.nih.gov/pubmed/14990650
- Cancer Chemother Pharmacol. 2004 Oct;54(4):290-4
- Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects.
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- Effect of St John's wort on imatinib mesylate pharmacokinetics.
- Clin Pharmacol Ther. 2004 Oct;76(4):323-9.
- PMID: 15470331 https://www.ncbi.nlm.nih.gov/pubmed/15470331
2005年
- Br J Clin Pharmacol. 2005 Jul;60(1):35-44
- Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study.
- PMID: 15963092 https://www.ncbi.nlm.nih.gov/pubmed/15963092
- Drug Metab Dispos. 2005 Oct;33(10):1503-12.
- Metabolism and disposition of imatinib mesylate in healthy volunteers.
- PMID: 16006570 https://www.ncbi.nlm.nih.gov/pubmed/16006570
- Oncology. 2005;69(5):363-71
- Pharmacokinetic and clinical phase II trial of imatinib in patients with impaired liver function and advanced hepatocellular carcinoma.
- PMID: 16319507 https://www.ncbi.nlm.nih.gov/pubmed/16319507
2006年
- Pharmacotherapy. 2006 Jul;26(7):903-7.
- Disposition of imatinib and its metabolite CGP74588 in a patient with chronic myelogenous leukemia and short-bowel syndrome.
- PMID: 16803422 https://www.ncbi.nlm.nih.gov/pubmed/16803422
- Clin Cancer Res. 2006 Aug 15;12(16):4899-907.
- Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08.
- PMID: 16914578 https://www.ncbi.nlm.nih.gov/pubmed/16914578
2007年
- Blood. 2007 Apr 15;109(8):3496-9.
- Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia.
- PMID: 17192396 https://www.ncbi.nlm.nih.gov/pubmed/17192396
- Clin Pharmacol Ther. 2007 Jul;82(1):33-40
- Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype.
- PMID: 17495881 https://www.ncbi.nlm.nih.gov/pubmed/17495881
- Clin Cancer Res. 2007 Oct 1;13(19):5876-82.
- Phase I and pharmacokinetic study of imatinib mesylate (Gleevec) and gemcitabine in patients with refractory solid tumors.
- PMID: 17908982 https://www.ncbi.nlm.nih.gov/pubmed/17908982
- Clin Cancer Res. 2007 Dec 15;13(24):7394-400.
- Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib.
- PMID: 18094422 https://www.ncbi.nlm.nih.gov/pubmed/18094422
2008年
- Cancer Lett. 2008 Feb 18;260(1-2):146-54
- Imatinib for hepatocellular cancer--focus on pharmacokinetic/pharmacodynamic modelling and liver function.
- PMID: 18083304 https://www.ncbi.nlm.nih.gov/pubmed/18083304
- J Clin Oncol. 2008 Feb 1;26(4):563-9. doi: 10.1200/JCO.2007.11.0304.
- Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group.
- PMID: 18235115 https://www.ncbi.nlm.nih.gov/pubmed/18235115
- Blood. 2008 Apr 15;111(8):4022-8.
- Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study.
- PMID: 18256322 https://www.ncbi.nlm.nih.gov/pubmed/18256322
2009年
- Cancer Chemother Pharmacol. 2009 Jan;63(2):229-38. doi: 10.1007/s00280-008-0730-x. Epub 2008 Apr 9.
- Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults.
- PMID: 18398615 https://www.ncbi.nlm.nih.gov/pubmed/18398615
- Cancer Chemother Pharmacol. 2009 Feb;63(3):525-8.
- Effect of antacid on imatinib absorption.
- PMID: 18500518 https://www.ncbi.nlm.nih.gov/pubmed/18500518
- J Clin Oncol. 2009 Jul 1;27(19):3141-7. doi: 10.1200/JCO.2008.20.4818. Epub 2009 May 18.
- Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors.
- PMID: 19451435 https://www.ncbi.nlm.nih.gov/pubmed/19451435
- Br J Clin Pharmacol. 2009 Sep;68(3):370-4. doi: 10.1111/j.1365-2125.2009.03466.x.
- Effect of a proton pump inhibitor on the pharmacokinetics of imatinib.
- PMID: 19740393 https://www.ncbi.nlm.nih.gov/pubmed/19740393
2010年
- J Neurooncol. 2010 Apr;97(2):241-5. doi: 10.1007/s11060-009-0008-0. Epub 2009 Sep 19.
- Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme.
- PMID: 19768386 https://www.ncbi.nlm.nih.gov/pubmed/19768386
- Acta Pharmacol Sin. 2010 Aug;31(8):999-1004. doi: 10.1038/aps.2010.79. Epub 2010 Jul 19.
- Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients.
- PMID: 20644548 https://www.ncbi.nlm.nih.gov/pubmed/20644548
2011年
- Cancer Chemother Pharmacol. 2011 Sep;68(3):643-51. doi: 10.1007/s00280-010-1530-7. Epub 2010 Dec 1.
- A phase I study of imatinib mesylate in combination with chlorambucil in previously treated chronic lymphocytic leukemia patients.
- PMID: 21120481 https://www.ncbi.nlm.nih.gov/pubmed/21120481
- Leuk Lymphoma. 2011 Jun;52(6):1024-9. doi: 10.3109/10428194.2011.563885. Epub 2011 Apr 4.
- Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia
- PMID: 21463107 https://www.ncbi.nlm.nih.gov/pubmed/21463107
- Pak J Pharm Sci. 2011 Jul;24(3):285-91.
- Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS.
- PMID: 21715261 https://www.ncbi.nlm.nih.gov/pubmed/21715261
2012年
- Invest New Drugs. 2012 Aug;30(4):1703-8. doi: 10.1007/s10637-011-9633-5. Epub 2011 Jan 14.
- Changes in imatinib plasma trough level during long-term treatment of patients with advanced gastrointestinal stromal tumors: correlation between changes in covariates and imatinib exposure.
- PMID: 21234641 https://www.ncbi.nlm.nih.gov/pubmed/21234641
- Haematologica. 2012 May;97(5):731-8. doi: 10.3324/haematol.2011.045666. Epub 2012 Feb 7.
- Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial.
- PMID: 22315495 https://www.ncbi.nlm.nih.gov/pubmed/22315495
2013年
- Br J Clin Pharmacol. 2013 Apr;75(4):1007-18
- Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.
- PMID: 22891806 https://www.ncbi.nlm.nih.gov/pubmed/22891806
2014年
- Cancer Chemother Pharmacol. 2014 Jul;74(1):85-93. doi: 10.1007/s00280-014-2473-1. Epub 2014 May 10.
- Population pharmacokinetics of imatinib in Iranian patients with chronic-phase chronic myeloid leukemia.
- PMID: 24817601 https://www.ncbi.nlm.nih.gov/pubmed/24817601
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