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Press:London, 1943; pp80\u2013117."},{"key":"ref11\/cit11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/194979a0","volume":"194","author":"Mueller P.","year":"1962","journal-title":"Nature"},{"key":"ref12\/cit12","unstructured":"Stein, W. D.The Movement of Molecules across Cell Membranes;Academic Press:New York, 1967; pp65\u2013125."},{"key":"ref13\/cit13","first-page":"881","volume":"79","author":"Gallucci E.","year":"1971","journal-title":"Arch. Int. Physiol. Biochim."},{"key":"ref14\/cit14","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1126\/science.182.4118.1258","volume":"182","author":"Gutknecht J.","year":"1973","journal-title":"Science"},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/0006-8993(79)90546-8","volume":"172","author":"Rapaport S. I.","year":"1979","journal-title":"Brain Res."},{"key":"ref16\/cit16","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1152\/physrev.1984.64.3.763","volume":"64","author":"Barry P. H.","year":"1984","journal-title":"Physiol. Rev."},{"key":"ref17\/cit17","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1246\/bcsj.60.4357","volume":"60","author":"Miyoshi H.","year":"1987","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref18\/cit18","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/bies.950171213","author":"Bangham A. D.","year":"1995","journal-title":"BioEssays"},{"key":"ref19\/cit19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s002320001019","volume":"173","author":"Xiang T.-X.","year":"2000","journal-title":"J. Membr. Biol."},{"key":"ref20\/cit20","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/cphc.200900270","volume":"10","author":"Missner A.","year":"2009","journal-title":"ChemPhysChem"},{"key":"ref21\/cit21","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s11095-010-0303-7","volume":"28","author":"Liu X.","year":"2011","journal-title":"Pharm. Res."},{"key":"ref22\/cit22","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1128\/AAC.00437-11","volume":"56","author":"Djukic M.","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref23\/cit23","first-page":"1","volume":"89","author":"Jin B.","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref24\/cit24","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1021\/jm200319u","volume":"54","author":"Oballa R. M.","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref25\/cit25","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1021\/jm2014887","volume":"55","author":"Pfefferkorn J. A.","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref26\/cit26","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/S0006-2952(98)00017-3","volume":"55","author":"Xu A. S. L.","year":"1998","journal-title":"Biochem. Pharmacol."},{"key":"ref27\/cit27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0378-5173(92)90260-9","volume":"80","author":"Tsai R. S.","year":"1992","journal-title":"Int. J. Pharmaceut."},{"key":"ref28\/cit28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1039\/cs9932200073","volume":"22","author":"Abraham M. H.","year":"1993","journal-title":"Chem. Soc. Rev."},{"key":"ref29\/cit29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0166-1280(99)00360-7","volume":"503","author":"Cruciani G.","year":"2000","journal-title":"J. Mol. Struct. 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Sci."},{"key":"ref35\/cit35","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1124\/jpet.102.039255","volume":"303","author":"Doan K. M.","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref36\/cit36","doi-asserted-by":"crossref","DOI":"10.1002\/9781118286067","volume-title":"Absorption and Drug Development","author":"Avdeef A.","year":"2012","edition":"2"},{"key":"ref37\/cit37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0022-3565(25)12995-9","volume":"125","author":"Hogben C. A.","year":"1959","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref38\/cit38","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ejps.2004.11.011","volume":"24","author":"Avdeef A.","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref39\/cit39","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11095-010-0280-x","volume":"28","author":"Tsinman O.","year":"2011","journal-title":"Pharm. Res."},{"key":"ref40\/cit40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejps.2009.06.009","volume":"38","author":"Dagenais C.","year":"2009","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref41\/cit41","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0031-6997(24)01329-2","volume":"49","author":"Hinderling P. H.","year":"1997","journal-title":"Pharmacol. Rev."},{"key":"ref42\/cit42","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2533\/chimia.1992.299","volume":"46","author":"van de Waterbeemd H.","year":"1992","journal-title":"Chimia"},{"key":"ref43\/cit43","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1211\/0022357991777164","volume":"51","author":"Pagliara A.","year":"1999","journal-title":"J. Pharm. Pharmacol."},{"key":"ref44\/cit44","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1023\/A:1025032511040","volume":"20","author":"Neuhoff S.","year":"2003","journal-title":"Pharm. Res."},{"key":"ref45\/cit45","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0925-4439(02)00074-1","volume":"1587","author":"Ooms F.","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref46\/cit46","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s11095-007-9502-2","volume":"25","author":"Hammarlund-Udenaes M.","year":"2008","journal-title":"Pharm. Res."},{"key":"ref47\/cit47","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/dmd.110.035998","volume":"39","author":"Frid\u00e9n M.","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref48\/cit48","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1124\/dmd.109.026674","volume":"37","author":"Liu X.","year":"2009","journal-title":"Drug Metab. Dispos."},{"key":"ref49\/cit49","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1046\/j.1365-2125.2001.01471.x","volume":"52","author":"Tagawa M.","year":"2001","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref50\/cit50","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/2061260a0","volume":"206","author":"Beckett A. H.","year":"1965","journal-title":"Nature"},{"key":"ref51\/cit51","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1749-6632.1971.tb46926.x","volume":"179","author":"Davis J. M.","year":"1971","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref52\/cit52","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/j.1365-2125.1982.tb02030.x","volume":"14","author":"Cham B. E.","year":"1982","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref53\/cit53","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1046\/j.1365-2125.1998.00819.x","volume":"46","author":"Freudenthaler S.","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref54\/cit54","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0733-8635(05)70011-5","volume":"16","author":"Kalia Y. N.","year":"1998","journal-title":"Clin. Asp. Dermatol. Ther."},{"key":"ref55\/cit55","first-page":"93","volume-title":"Principles of Route-to-Route Extrapolation for Risk Assessment","author":"Flynn G. L.","year":"1990"},{"key":"ref56\/cit56","first-page":"239","volume-title":"Modern Pharmaceutics","author":"Flynn G. L.","year":"1996"},{"key":"ref57\/cit57","first-page":"39","volume":"10","author":"Ritschel W. A.","year":"1988","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref58\/cit58","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/jidsymp.1998.27","volume":"3","author":"Hadgraft J.","year":"1998","journal-title":"J. Invest. Dermatol."},{"key":"ref59\/cit59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0022-2275(20)38006-8","volume":"24","author":"Lampe M. A.","year":"1983","journal-title":"J. Lipid Res."},{"key":"ref60\/cit60","first-page":"702","volume":"51","author":"Scheuplein R. J.","year":"1971","journal-title":"Pharmacol. Rev."},{"key":"ref61\/cit61","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.2042-7158.1979.tb13456.x","volume":"31","author":"Albery W. J.","year":"1979","journal-title":"J. Pharm. Pharmacol."},{"key":"ref62\/cit62","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1023\/A:1016048710880","volume":"13","author":"Heisig M.","year":"1996","journal-title":"Pharm. Res."},{"key":"ref63\/cit63","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1177\/28.6.7190175","volume":"28","author":"Nemanic M. K.","year":"1980","journal-title":"J. Histochem. Cytochem."},{"key":"ref64\/cit64","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1023\/A:1011986613392","volume":"15","author":"Mouritsen O. G.","year":"1998","journal-title":"Pharm. Res."},{"key":"ref65\/cit65","unstructured":"www.drugbank.ca."},{"key":"ref66\/cit66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0378-5173(95)04278-4","volume":"132","author":"Roberts M. 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