{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:48:02Z","timestamp":1788536882325,"version":"build-2803163510"},"reference-count":34,"publisher":"Pharmaceutical Society of Japan","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological & Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2020,3,1]]},"DOI":"10.1248\/bpb.b19-00641","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T22:03:09Z","timestamp":1572645789000},"page":"384-392","source":"Crossref","is-referenced-by-count":5,"title":["Estimating Efflux Transporter-Mediated Disposition of Molecules beyond the Rule of Five (bRo5) Using Transporter Gene Knockout Rats"],"prefix":"10.1248","volume":"43","author":[{"given":"Taiji","family":"Miyake","sequence":"first","affiliation":[{"name":"Discovery ADMET Dept., Research Div., Chugai Pharmaceutical Co., Ltd."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","unstructured":"1) Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev.<\/i>, 46<\/b>, 3\u201326 (2001)."},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Matsson P, Doak BC, Over B, Kihlberg J. Cell permeability beyond the rule of 5. Adv. Drug Deliv. Rev.<\/i>, 101<\/b>, 42\u201361 (2016).","DOI":"10.1016\/j.addr.2016.03.013"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab. Rev.<\/i>, 34<\/b>, 47\u201354 (2002).","DOI":"10.1081\/DMR-120001389"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Giacomini KM, Huang SM, Tweedie DJ, et al.<\/i> Membrane transporters in drug development. Nat. Rev. Drug Discov.<\/i>, 9<\/b>, 215\u2013236 (2010).","DOI":"10.1038\/nrd3028"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Zamek-Gliszczynski MJ, Lee CA, Poirier A, Bentz J, Chu X, Ellens H, Ishikawa T, Jamei M, Kalvass JC, Nagar S, Pang KS, Korzekwa K, Swaan PW, Taub ME, Zhao P, Galetin A. ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans. Clin. Pharmacol. Ther.<\/i>, 94<\/b>, 64\u201379 (2013).","DOI":"10.1038\/clpt.2013.45"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Cao X, Gibbs ST, Fang L, Miller HA, Landowski CP, Shin HC, Lennernas H, Zhong Y, Amidon GL, Yu LX, Sun D. Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. Pharm. Res.<\/i>, 23<\/b>, 1675\u20131686 (2006).","DOI":"10.1007\/s11095-006-9041-2"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Zamek-Gliszczynski MJ, Goldstein KM, Paulman A, Baker TK, Ryan TP. Minor compensatory changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats do not detract from their utility in the study of transporter-mediated pharmacokinetics. Drug Metab. Dispos.<\/i>, 41<\/b>, 1174\u20131178 (2013).","DOI":"10.1124\/dmd.113.051409"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Zamek-Gliszczynski MJ, Bedwell DW, Bao JQ, Higgins JW. Characterization of SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats using loperamide, paclitaxel, sulfasalazine, and carboxydichlorofluorescein pharmacokinetics. Drug Metab. Dispos.<\/i>, 40<\/b>, 1825\u20131833 (2012).","DOI":"10.1124\/dmd.112.046508"},{"key":"9","unstructured":"9) Suzuki M, Komura H, Yoshikawa T, Enya S, Nagao A, Takubo H, Kogayu M. Characterization of gastrointestinal absorption of digoxin involving influx and efflux transporter in rats: application of mdr1a knockout (\u2212\/\u2212) rats into absorption study of multiple transporter substrate. Xenobiotica<\/i>, 44<\/b>, 1039\u20131045 (2014)."},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Fuchs H, Kishimoto W, Gansser D, Tanswell P, Ishiguro N. Brain penetration of WEB 2086 (Apafant) and dantrolene in Mdr1a (P-glycoprotein) and Bcrp knockout rats. Drug Metab. Dispos.<\/i>, 42<\/b>, 1761\u20131765 (2014).","DOI":"10.1124\/dmd.114.058545"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Bundgaard C, Jensen CJ, Garmer M. Species comparison of in vivo<\/i> P-glycoprotein-mediated brain efflux using mdr1a-deficient rats and mice. Drug Metab. Dispos.<\/i>, 40<\/b>, 461\u2013466 (2012).","DOI":"10.1124\/dmd.111.043083"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Brennan BJ, Moreira SA, Morcos PN, Navarro MT, Asthappan J, Goelzer P, Weigl P, Smith PF. Pharmacokinetics of a three-way drug interaction between danoprevir, ritonavir and the organic anion transporting polypeptide (OATP) inhibitor ciclosporin. Clin. Pharmacokinet.<\/i>, 52<\/b>, 805\u2013813 (2013).","DOI":"10.1007\/s40262-013-0077-2"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) German P, Mathias A, Brainard D, Kearney BP. Clinical pharmacokinetics and pharmacodynamics of Ledipasvir\/Sofosbuvir, a fixed-dose combination tablet for the treatment of hepatitis C. Clin. Pharmacokinet.<\/i>, 55<\/b>, 1337\u20131351 (2016).","DOI":"10.1007\/s40262-016-0397-0"},{"key":"14","unstructured":"14) Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev.<\/i>, 55<\/b>, 3\u201329 (2003)."},{"key":"15","unstructured":"15) Company BMS. Sunvepra Capsules (asunaprevir) Japanese Prescribing Information.<\/i> (2014)."},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther.<\/i>, 52<\/b>, 453\u2013457 (1992).","DOI":"10.1038\/clpt.1992.171"},{"key":"17","unstructured":"17) Reddy MB, Chen Y, Haznedar JO, Fretland J, Blotner S, Smith P, Tran JQ. Impact of low-dose ritonavir on danoprevir pharmacokinetics: results of computer-based simulations and a clinical drug-drug interaction study. Clin. Pharmacokinet.<\/i>, 51<\/b>, 457\u2013465 (2012)."},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Brennan BJ, Poirier A, Moreira S, Morcos PN, Goelzer P, Portmann R, Asthappan J, Funk C, Smith PF. Characterization of the transmembrane transport and absolute bioavailability of the HCV protease inhibitor danoprevir. Clin. Pharmacokinet.<\/i>, 54<\/b>, 537\u2013549 (2015).","DOI":"10.1007\/s40262-014-0222-6"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) German P, Mathias A, Brainard DM, Kearney BP. Drug-drug interaction profile of the fixed-dose combination tablet regimen Ledipasvir\/Sofosbuvir. Clin. Pharmacokinet.<\/i>, 57<\/b>, 1369\u20131383 (2018).","DOI":"10.1007\/s40262-018-0654-5"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Ouwerkerk-Mahadevan S, Snoeys J, Peeters M, Beumont-Mauviel M, Simion A. Drug-drug interactions with the NS3\/4A protease inhibitor Simeprevir. Clin. Pharmacokinet.<\/i>, 55<\/b>, 197\u2013208 (2016).","DOI":"10.1007\/s40262-015-0314-y"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 84<\/b>, 7735\u20137738 (1987).","DOI":"10.1073\/pnas.84.21.7735"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Cordon-Cardo C, O\u2019Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem.<\/i>, 38<\/b>, 1277\u20131287 (1990).","DOI":"10.1177\/38.9.1974900"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Lin JH, Yamazaki M. Clinical relevance of P-glycoprotein in drug therapy. Drug Metab. Rev.<\/i>, 35<\/b>, 417\u2013454 (2003).","DOI":"10.1081\/DMR-120026871"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Cao X, Yu LX, Barbaciru C, Landowski CP, Shin HC, Gibbs S, Miller HA, Amidon GL, Sun D. Permeability dominates in vivo<\/i> intestinal absorption of P-gp substrate with high solubility and high permeability. Mol. Pharm.<\/i>, 2<\/b>, 329\u2013340 (2005).","DOI":"10.1021\/mp0499104"},{"key":"25","unstructured":"25) Dahan A, Amidon GL. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs. Mol. Pharm.<\/i>, 6<\/b>, 19\u201328 (2009)."},{"key":"26","unstructured":"26) Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro<\/i> drug product dissolution and in vivo<\/i> bioavailability. Pharm. Res.<\/i>, 12<\/b>, 413\u2013420 (1995)."},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Weiss J, Becker JP, Haefeli WE. Telaprevir is a substrate and moderate inhibitor of P-glycoprotein, a strong inductor of ABCG2, but not an activator of PXR in vitro.<\/i> Int. J. Antimicrob. Agents<\/i>, 43<\/b>, 184\u2013188 (2014).","DOI":"10.1016\/j.ijantimicag.2013.10.003"},{"key":"28","unstructured":"28) Bleasby K, Castle JC, Roberts CJ, Cheng C, Bailey WJ, Sina JF, Kulkarni AV, Hafey MJ, Evers R, Johnson JM, Ulrich RG, Slatter JG. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica<\/i>, 36<\/b>, 963\u2013988 (2006)."},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Katoh M, Suzuyama N, Takeuchi T, Yoshitomi S, Asahi S, Yokoi T. Kinetic analyses for species differences in P-glycoprotein-mediated drug transport. J. Pharm. Sci.<\/i>, 95<\/b>, 2673\u20132683 (2006).","DOI":"10.1002\/jps.20686"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Takeuchi T, Yoshitomi S, Higuchi T, Ikemoto K, Niwa S, Ebihara T, Katoh M, Yokoi T, Asahi S. Establishment and characterization of the transformants stably-expressing MDR1 derived from various animal species in LLC-PK1. Pharm. Res.<\/i>, 23<\/b>, 1460\u20131472 (2006).","DOI":"10.1007\/s11095-006-0285-7"},{"key":"31","unstructured":"31) Yamasaki Y, Kobayashi K, Okuya F, Kajitani N, Kazuki K, Abe S, Takehara S, Ito S, Ogata S, Uemura T, Ohtsuki S, Minegishi G, Akita H, Chiba K, Oshimura M, Kazuki Y. Characterization of P-glycoprotein humanized mice generated by chromosome engineering technology: its utility for prediction of drug distribution to the brain in humans. Drug Metab. Dispos.<\/i>, 46<\/b>, 1756\u20131766 (2018)."},{"key":"32","unstructured":"32) Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet.<\/i>, 42<\/b>, 59\u201398 (2003)."},{"key":"33","unstructured":"33) Eley T, Garimella T, Li W, Bertz RJ. Asunaprevir: a review of preclinical and clinical pharmacokinetics and drug\u2013drug interactions. Clin. Pharmacokinet.<\/i>, 54<\/b>, 1205\u20131222 (2015)."},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Garg V, van Heeswijk R, Lee JE, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology<\/i>, 54<\/b>, 20\u201327 (2011).","DOI":"10.1002\/hep.24443"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/3\/43_b19-00641\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T03:19:36Z","timestamp":1583551176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/43\/3\/43_b19-00641\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,1]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b19-00641","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,1]]}}}