研究内容

PK/PD & TDM

• 薬物動態と薬効の定量的Modeling & Simulation
• 臨床における個人差のモデル化
• 個別化投薬アルゴリズム

代表論文

• The Effects of Advanced Age and Serum α1 -Acid Glycoprotein on Docetaxel Unbound Exposure and Dose-limiting Toxicity in Cancer Patients.
  Kenmotsu H, Imamura CK, Ono A, Omori S, Nakashima K, Wakuda K, Taira T, Naito T, Murakami H, Takahashi T, Tanigawara Y.
  Br J Clin Pharmacol. 2017 Jun 22. doi: 10.1111/bcp.13354. [Epub ahead of print]
• Development of an S-1 dosage formula based on renal function by a prospective pharmacokinetic study.
  Booka E, Imamura CK, Takeuchi H, Hamamoto Y, Gomi D, Mizukami T, Ichiyama T, Tateishi K, Takahashi T, Kawakubo H, Soejima K, Boku N, Tanigawara Y, Kitagawa Y.
  Gastric Cancer. 2016 Jul;19(3):876-86. doi: 10.1007/s10120-015-0536-6. Epub 2015 Aug 25.
• Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose.
  Kenmotsu H, Tanigawara Y.
  Cancer Sci. 2015 May;106(5):497-504. doi: 10.1111/cas.12647. Epub 2015 Mar 25. Review.
• Optimal dose finding of garenoxacin based on population pharmacokinetics/pharmacodynamics and Monte Carlo simulation.
  Tanigawara Y, Nozawa K, Tsuda H.
  Eur J Clin Pharmacol. 2012 Jan;68(1):39-53. doi: 10.1007/s00228-011-1095-3. Epub 2011 Jul 28.
• Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations.
  Ohata Y, Tomita Y, Nakayama M, Kozuki T, Sunakawa K, Tanigawara Y.
  Drug Metab Pharmacokinet. 2011;26(5):523-31. Epub 2011 Jul 12.
• Population pharmacokinetics of Arbekacin in patients infected with methicillin-resistant Staphylococcus aureus.
  Tanigawara Y, Sato R, Morita K, Kaku M, Aikawa N, Shimizu K.
  Antimicrob Agents Chemother. 2006 Nov;50(11):3754-62.
• Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western and Japanese patients.
  Comets E, Ikeda K, Hoff P, Fumoleau P, Wanders J, Tanigawara Y.
  J Pharmacokinet Pharmacodyn. 2003 Aug;30(4):257-83.
• Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1).
  Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R.
  J Pharmacol Exp Ther. 1992 Nov;263(2):840-5.
• A pharmacokinetic analysis program (multi) for microcomputer.
  Yamaoka K, Tanigawara Y, Nakagawa T, Uno T.
  J Pharmacobiodyn. 1981 Nov;4(11):879-85.

Pharmacogenomics

• 薬物動態・薬効と関連する遺伝子多型
• 遺伝子マーカーを利用する個別化投薬

代表論文

• Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole.
  Imamura CK, Furihata K, Okamoto S, Tanigawara Y.
  J Clin Pharmacol. 2016 Apr;56(4):408-13. doi: 10.1002/jcph.605. Epub 2015 Oct 8.
• Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients.
  Kiyotani K, Mushiroda T, Imamura CK, Tanigawara Y, Hosono N, Kubo M, Sasa M, Nakamura Y, Zembutsu H.
  Breast Cancer Res Treat. 2012 Jan;131(1):137-45. doi: 10.1007/s10549-011-1777-7. Epub 2011 Sep 23.
• Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients.
  Kiyotani K, Mushiroda T, Imamura CK, Hosono N, Tsunoda T, Kubo M, Tanigawara Y, Flockhart DA, Desta Z, Skaar TC, Aki F, Hirata K, Takatsuka Y, Okazaki M, Ohsumi S, Yamakawa T, Sasa M, Nakamura Y, Zembutsu H.
  J Clin Oncol. 2010 Mar 10;28(8):1287-93. doi: 10.1200/JCO.2009.25.7246. Epub 2010 Feb 1.
• A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam.
  Kosaki K, Tamura K, Sato R, Samejima H, Tanigawara Y, Takahashi T.
  Brain Dev. 2004 Dec;26(8):530-4.
• CYP2C19 genotype-related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori.
  Tanigawara Y, Aoyama N, Kita T, Shirakawa K, Komada F, Kasuga M, Okumura K.
  Clin Pharmacol Ther. 1999 Nov;66(5):528-34.
• Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism.
  Okumura K, Kita T, Chikazawa S, Komada F, Iwakawa S, Tanigawara Y.
  Clin Pharmacol Ther. 1997 May;61(5):509-17.

Pharmacoproteomics

• 薬物反応と関連するタンパク質発現
• 薬効を反映するバイオマーカー

代表論文

• Forced expression of S100A10 reduces sensitivity to oxaliplatin in colorectal cancer cells.
  Suzuki S, Tanigawara Y.
  Proteome Sci. 2014 May 9;12:26. doi: 10.1186/1477-5956-12-26. eCollection 2014.
• S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells.
  Suzuki S, Yamayoshi Y, Nishimuta A, Tanigawara Y.
  Proteome Sci. 2011 Dec 30;9:76. doi: 10.1186/1477-5956-9-76.

Pharmacometabolomics

• 薬物作用に対する代謝応答の解明
• 薬効を反映する代謝マーカーの探索

代表論文

• Effect of everolimus on the glucose metabolic pathway in mouse skeletal muscle cells (C2C12).
  Yoshida K, Imamura CK, Hara K, Mochizuki M, Tanigawara Y.
  Metabolomics. 2017;13(8):98. doi: 10.1007/s11306-017-1236-5. Epub 2017 Jul 7.