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Napp Napp

Nappは樋坂が開発した薬物動態解析などのモデリング・シミュレーションのためのソフトウェアです。詳細は以前のバージョンのマニュアルを参照ください。また、Nappを使用した研究の以下の論文リストを参考にしてください。このリストは今後更新されます。Nappの動作にはApple MacOSの環境が必要です。 Napp(3.071β)は2023年7月31日で動作を停止していますが、このバージョンの継続使用を希望する方は、メニューの「Nappについて」で開くパネルに表示される申請キーを、napp(at)ml.chiba-u.jpにメール本文に含めて送ってください。メールの表題は「Napp期間延長」としてください。折返し3ヶ月試用期間が延長される入力キーを提供します。なお、母集団解析の結果などが改善されたNapp(3.08)を、無料で近日中に公開予定です。


最新バージョンのダウンロード (Version 3.071β)

以前のバージョンのマニュアル (Version 2.01)

以前のバージョンのダウンロード(Version 2.31)

以前のバージョンのダウンロード(Version 2.01)


問い合わせは E-mail: napp(at) まで。ただし、返信できない場合、あるいは返信に時間を要する場合があります。


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  2. Iwatsubo T, Hisaka A, Suzuki H, Sugiyama Y. Prediction of in vivo nonlinear first-pass hepatic metabolism of YM796 from in vitro metabolic data. J Pharmacol Exp Ther. 1998 Jul;286(1):122-7. PMID: 9655850.
  3. Hisaka A, Sugiyama Y. Notes on the inverse Gaussian distribution and choice of boundary conditions for the dispersion model in the analysis of local pharmacokinetics. J Pharm Sci. 1999 Dec;88(12):1362-5. doi: 10.1021/js9803860. PMID: 10585235.
  4. Hisaka A, Nakamura T, Sugiyama Y. Analysis of nonlinear hepatic clearance of a cyclopentapeptide, BQ-123, with the multiple indicator dilution method using the dispersion model. Pharm Res. 1999 Jan;16(1):103-9. doi: 10.1023/a:1018831131119. PMID: 9950287.
  5. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y. A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5-FU. Pharm Res. 2001 Aug;18(8):1190-202. doi: 10.1023/a:1010939329562. PMID: 11587492.
  6. Tsukamoto Y, Kato Y, Ura M, Horii I, Ishikawa T, Ishitsuka H, Sugiyama Y. Investigation of 5-FU disposition after oral administration of capecitabine, a triple-prodrug of 5-FU, using a physiologically based pharmacokinetic model in a human cancer xenograft model: comparison of the simulated 5-FU exposures in the tumour tissue between human and xenograft model. Biopharm Drug Dispos. 2001 Jan;22(1):1-14. doi: 10.1002/bdd.250. PMID: 11745902.
  7. Mizuno N, Kato Y, Iwamoto M, Urae A, Amamoto T, Niwa T, Sugiyama Y. Kinetic analysis of the disposition of insulin-like growth factor 1 in healthy volunteers. Pharm Res. 2001 Aug;18(8):1203-9. doi: 10.1023/a:1010991313633. PMID: 11587493.
  8. Sato H, Kato Y, Hayasi E, Tabata T, Suzuki M, Takahara Y, Sugiyama Y. A novel hepatic-targeting system for therapeutic cytokines that delivers to the hepatic asialoglycoprotein receptor, but avoids receptor-mediated endocytosis. Pharm Res. 2002 Nov;19(11):1736-44. doi: 10.1023/a:1020773800358. Erratum in: Pharm Res. 2003 Apr;20(4):701. PMID: 12458681.
  9. 樋坂章博. 薬物動態解析プログラムNappの紹介. 薬剤学, 71, 168-178, 2011.
  10. Kudo T, Hisaka A, Sugiyama Y, Ito K. Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes. Drug Metab Dispos. 2013 Feb;41(2):362-71. doi: 10.1124/dmd.112.049460. Epub 2012 Nov 8. PMID: 23139378.
  11. Sugiura T, Takahashi S, Sano K, Abe T, Fukuta K, Adachi K, Nakamura T, Matsumoto K, Nakamichi N, Kato Y. Pharmacokinetic modeling of hepatocyte growth factor in experimental animals and humans. J Pharm Sci. 2013 Jan;102(1):237-49. doi: 10.1002/jps.23337. Epub 2012 Oct 9. PMID: 23047829.
  12. Takeuchi K, Sugiura T, Matsubara K, Sato R, Shimizu T, Masuo Y, Horikawa M, Nakamichi N, Ishiwata N, Kato Y. Interaction of novel platelet-increasing agent eltrombopag with rosuvastatin via breast cancer resistance protein in humans. Drug Metab Dispos. 2014 Apr;42(4):726-34. doi: 10.1124/dmd.113.054767. Epub 2014 Jan 17. PMID: 24440960.
  13. Shirota K, Kaneko M, Sasaki M, Minato K, Fujikata A, Ohta S, Hisaka A, Suzuki H. Analysis of the disposition of a novel p38 MAPK inhibitor, AKP-001, and its metabolites in rats with a simple physiologically based pharmacokinetic model. Drug Metab Dispos. 2015 Feb;43(2):217-26. doi: 10.1124/dmd.114.060046. Epub 2014 Nov 24. PMID: 25422274.
  14. Ando H, Hisaka A, Suzuki H. A new physiologically based pharmacokinetic model for the prediction of gastrointestinal drug absorption: translocation model. Drug Metab Dispos. 2015 Apr;43(4):590-602. doi: 10.1124/dmd.114.060038. Epub 2015 Jan 23. PMID: 25616403.
  15. Fujita K, Masuo Y, Okumura H, Watanabe Y, Suzuki H, Sunakawa Y, Shimada K, Kawara K, Akiyama Y, Kitamura M, Kunishima M, Sasaki Y, Kato Y. Increased Plasma Concentrations of Unbound SN-38, the Active Metabolite of Irinotecan, in Cancer Patients with Severe Renal Failure. Pharm Res. 2016 Feb;33(2):269-82. doi: 10.1007/s11095-015-1785-0. Epub 2015 Sep 3. PMID: 26337772.
  16. Yoshikado T, Yoshida K, Kotani N, Nakada T, Asaumi R, Toshimoto K, Maeda K, Kusuhara H, Sugiyama Y. Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method. Clin Pharmacol Ther. 2016 Nov;100(5):513-523. doi: 10.1002/cpt.391. Epub 2016 Jul 28. PMID: 27170342.
  17. Ando H, Hatakeyama H, Sato H, Hisaka A, Suzuki H. Determinants of Intestinal Availability for P-glycoprotein Substrate Drugs Estimated by Extensive Simulation With Mathematical Absorption Models. J Pharm Sci. 2017 Sep;106(9):2771-2779. doi: 10.1016/j.xphs.2017.04.065. Epub 2017 May 4. PMID: 28479352.
  18. Kudo T, Goda H, Yokosuka Y, Tanaka R, Komatsu S, Ito K. Estimation of the Contribution of CYP2C8 and CYP3A4 in Repaglinide Metabolism by Human Liver Microsomes Under Various Buffer Conditions. J Pharm Sci. 2017 Sep;106(9):2847-2852. doi: 10.1016/j.xphs.2017.02.013. Epub 2017 Feb 24. PMID: 28238899.
  19. Yoshikado T, Maeda K, Kusuhara H, Furihata KI, Sugiyama Y. Quantitative Analyses of the Influence of Parameters Governing Rate-Determining Process of Hepatic Elimination of Drugs on the Magnitudes of Drug-Drug Interactions via Hepatic OATPs and CYP3A Using Physiologically Based Pharmacokinetic Models. J Pharm Sci. 2017 Sep;106(9):2739-2750. doi: 10.1016/j.xphs.2017.05.001. Epub 2017 May 8. PMID: 28495568.
  20. Kim SJ, Toshimoto K, Yao Y, Yoshikado T, Sugiyama Y. Quantitative Analysis of Complex Drug-Drug Interactions Between Repaglinide and Cyclosporin A/Gemfibrozil Using Physiologically Based Pharmacokinetic Models With In Vitro Transporter/Enzyme Inhibition Data. J Pharm Sci. 2017 Sep;106(9):2715-2726. doi: 10.1016/j.xphs.2017.04.063. Epub 2017 May 4. PMID: 28479356.
  21. Fukuchi Y, Toshimoto K, Mori T, Kakimoto K, Tobe Y, Sawada T, Asaumi R, Iwata T, Hashimoto Y, Nunoya KI, Imawaka H, Miyauchi S, Sugiyam Y. Analysis of Nonlinear Pharmacokinetics of a Highly Albumin-Bound Compound: Contribution of Albumin-Mediated Hepatic Uptake Mechanism. J Pharm Sci. 2017 Sep;106(9):2704-2714. doi: 10.1016/j.xphs.2017.04.052. Epub 2017 Apr 30. PMID: 28465151.
  22. Futatsugi A, Toshimoto K, Yoshikado T, Sugiyama Y, Kato Y. Evaluation of Alteration in Hepatic and Intestinal BCRP Function In Vivo from ABCG2 c.421C>A Polymorphism Based on PBPK Analysis of Rosuvastatin. Drug Metab Dispos. 2018 May;46(5):749-757. doi: 10.1124/dmd.117.078816. Epub 2018 Feb 12. PMID: 29440178.
  23. Sato M, Toshimoto K, Tomaru A, Yoshikado T, Tanaka Y, Hisaka A, Lee W, Sugiyama Y. Physiologically Based Pharmacokinetic Modeling of Bosentan Identifies the Saturable Hepatic Uptake As a Major Contributor to Its Nonlinear Pharmacokinetics. Drug Metab Dispos. 2018 May;46(5):740-748. doi: 10.1124/dmd.117.078972. Epub 2018 Feb 23. PMID: 29475833.
  24. Yoshikado T, Toshimoto K, Maeda K, Kusuhara H, Kimoto E, Rodrigues AD, Chiba K, Sugiyama Y. PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3. CPT Pharmacometrics Syst Pharmacol. 2018 Nov;7(11):739-747. doi: 10.1002/psp4.12348. Epub 2018 Sep 30. PMID: 30175555; PMCID: PMC6263667.
  25. Yao Y, Toshimoto K, Kim SJ, Yoshikado T, Sugiyama Y. Quantitative Analysis of Complex Drug-Drug Interactions between Cerivastatin and Metabolism/Transport Inhibitors Using Physiologically Based Pharmacokinetic Modeling. Drug Metab Dispos. 2018 Jul;46(7):924-933. doi: 10.1124/dmd.117.079210. Epub 2018 Apr 30. PMID: 29712725.
  26. Asaumi R, Toshimoto K, Tobe Y, Hashizume K, Nunoya KI, Imawaka H, Lee W, Sugiyama Y. Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug-Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects. CPT Pharmacometrics Syst Pharmacol. 2018 Mar;7(3):186-196. doi: 10.1002/psp4.12275. Epub 2018 Feb 5. PMID: 29368402; PMCID: PMC5869557.
  27. Ishida T, Tokuda K, Hisaka A, Honma M, Kijima S, Takatoku H, Iwatsubo T, Moritoyo T, Suzuki H; Alzheimer's Disease Neuroimaging Initiative. A Novel Method to Estimate Long-Term Chronological Changes From Fragmented Observations in Disease Progression. Clin Pharmacol Ther. 2019 Feb;105(2):436-447. doi: 10.1002/cpt.1166. Epub 2018 Aug 20. PMID: 29951994; PMCID: PMC6617977.
  28. Lee N, Maeda K, Fukizawa S, Ieiri I, Tomaru A, Akao H, Takeda K, Iwadare M, Niwa O, Masauji T, Yamane N, Kajinami K, Kusuhara H, Sugiyama Y. Microdosing clinical study to clarify pharmacokinetic and pharmacogenetic characteristics of atorvastatin in Japanese hypercholesterolemic patients. Drug Metab Pharmacokinet. 2019 Dec;34(6):387-395. doi: 10.1016/j.dmpk.2019.08.004. Epub 2019 Aug 29. PMID: 31594719.
  29. Nishiyama K, Toshimoto K, Lee W, Ishiguro N, Bister B, Sugiyama Y. Physiologically-Based Pharmacokinetic Modeling Analysis for Quantitative Prediction of Renal Transporter-Mediated Interactions Between Metformin and Cimetidine. CPT Pharmacometrics Syst Pharmacol. 2019 Jun;8(6):396-406. doi: 10.1002/psp4.12398. Epub 2019 Mar 19. Erratum in: CPT Pharmacometrics Syst Pharmacol. 2020 Oct;9(10):606-608. PMID: 30821133; PMCID: PMC6617824.
  30. Arakawa H, Sugiura S, Kawanishi T, Shin K, Toyoda H, Satoh T, Sakai Y, Kanamori T, Kato Y. Kinetic analysis of sequential metabolism of triazolam and its extrapolation to humans using an entero-hepatic two-organ microphysiological system. Lab Chip. 2020 Feb 7;20(3):537-547. doi: 10.1039/c9lc00884e. Epub 2020 Jan 13. PMID: 31930237.
  31. Asano S, Yoshitomo A, Hozuki S, Sato H, Kazuki Y, Hisaka A. A New Intestinal Model for Analysis of Drug Absorption and Interactions Considering Physiological Translocation of Contents. Drug Metab Dispos. 2021 Jul;49(7):581-591. doi: 10.1124/dmd.121.000361. Epub 2021 May 7. PMID: 33962977.
  32. Yoshikado T, Lee W, Toshimoto K, Morita K, Kiriake A, Chu X, Lee N, Kimoto E, Varma MVS, Kikuchi R, Scialis RJ, Shen H, Ishiguro N, Lotz R, Li AP, Maeda K, Kusuhara H, Sugiyama Y. Evaluation of Hepatic Uptake of OATP1B Substrates by Short Term-Cultured Plated Human Hepatocytes: Comparison With Isolated Suspended Hepatocytes. J Pharm Sci. 2021 Jan;110(1):376-387. doi: 10.1016/j.xphs.2020.10.041. Epub 2020 Oct 27. PMID: 33122051.
  33. Park JE, Shitara Y, Lee W, Morita S, Sahi J, Toshimoto K, Sugiyama Y. Improved Prediction of the Drug-Drug Interactions of Pemafibrate Caused by Cyclosporine A and Rifampicin via PBPK Modeling: Consideration of the Albumin-Mediated Hepatic Uptake of Pemafibrate and Inhibition Constants With Preincubation Against OATP1B. J Pharm Sci. 2021 Jan;110(1):517-528. doi: 10.1016/j.xphs.2020.10.016. Epub 2020 Oct 13. PMID: 33058894.
  34. Yoshitomo A, Asano S, Hozuki S, Tamemoto Y, Shibata Y, Hashimoto N, Takahashi K, Sasaki Y, Ozawa N, Kageyama M, Iijima T, Kazuki Y, Sato H, Hisaka A. Significance of Basal Membrane Permeability of Epithelial Cells in Predicting Intestinal Drug Absorption. Drug Metab Dispos. 2023 Mar;51(3):318-328. doi: 10.1124/dmd.122.000907. Epub 2022 Dec 7. PMID: 36810197.
  35. Matsumoto T, Masuo Y, Tanaka A, Kimura T, Ioroi T, Yamakawa T, Kitahara H, Kato Y. A physiologically based pharmacokinetic and pharmacodynamic model for disposition of FF-10832. Int J Pharm. 2022 Nov 5;627:122250. doi: 10.1016/j.ijpharm.2022.122250. Epub 2022 Sep 29. PMID: 36183917.
  36. Mochizuki T, Aoki Y, Yoshikado T, Yoshida K, Lai Y, Hirabayashi H, Yamaura Y, Rockich K, Taskar K, Takashima T, Chu X, Zamek-Gliszczynski MJ, Mao J, Maeda K, Furihata K, Sugiyama Y, Kusuhara H. Physiologically-based pharmacokinetic model-based translation of OATP1B-mediated drug-drug interactions from coproporphyrin I to probe drugs. Clin Transl Sci. 2022 Jun;15(6):1519-1531. doi: 10.1111/cts.13272. Epub 2022 May 2. PMID: 35421902; PMCID: PMC9199885.