{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:26:07Z","timestamp":1782987967186,"version":"3.54.5"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2012,9,19]],"date-time":"2012-09-19T00:00:00Z","timestamp":1348012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2013,3]]},"DOI":"10.1007\/s00228-012-1403-6","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T08:37:39Z","timestamp":1347957459000},"page":"523-532","source":"Crossref","is-referenced-by-count":28,"title":["Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects"],"prefix":"10.1007","volume":"69","author":[{"given":"Matthias","family":"Hoch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hoever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Alessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Theodor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,9,19]]},"reference":[{"issue":"3","key":"1403_CR1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrn2092","volume":"8","author":"T Sakurai","year":"2007","unstructured":"Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8(3):171\u2013181","journal-title":"Nat Rev Neurosci"},{"issue":"2","key":"1403_CR2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1124\/pr.109.001321","volume":"61","author":"N Tsujino","year":"2009","unstructured":"Tsujino N, Sakurai T (2009) Orexin\/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61(2):162\u2013176","journal-title":"Pharmacol Rev"},{"issue":"4","key":"1403_CR3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","volume":"92","author":"T Sakurai","year":"1998","unstructured":"Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92(4):573\u2013585","journal-title":"Cell"},{"issue":"1","key":"1403_CR4","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1073\/pnas.95.1.322","volume":"95","author":"L Lecea de","year":"1998","unstructured":"de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS 2nd, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95(1):322\u2013327","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"1403_CR5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1124\/pr.58.1.4","volume":"58","author":"R Spinazzi","year":"2006","unstructured":"Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG (2006) Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Pharmacol Rev 58(1):46\u201357","journal-title":"Pharmacol Rev"},{"issue":"2","key":"1403_CR6","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nm1544","volume":"13","author":"C Brisbare-Roch","year":"2007","unstructured":"Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, Mueller C, Nayler O, van Gerven J, de Haas SL, Hess P, Qiu C, Buchmann S, Scherz M, Weller T, Fischli W, Clozel M, Jenck F (2007) Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13(2):150\u2013155","journal-title":"Nat Med"},{"issue":"5","key":"1403_CR7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/clpt.2010.19","volume":"87","author":"P Hoever","year":"2010","unstructured":"Hoever P, de Haas S, Winkler J, Schoemaker RC, Chiossi E, van Gerven J, Dingemanse J (2010) Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin Pharmacol Ther 87(5):593\u2013600","journal-title":"Clin Pharmacol Ther"},{"key":"1403_CR8","doi-asserted-by":"crossref","unstructured":"Hoever P, de Haas S, Winkler J, Schoemaker RC, Chiossi E, van Gerven J, Dingemanse J Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin Pharmacol Ther 87 (5):593\u2013600","DOI":"10.1038\/clpt.2010.19"},{"issue":"1\u20132","key":"1403_CR9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3109\/01677063.2011.566953","volume":"25","author":"CJ Winrow","year":"2011","unstructured":"Winrow CJ, Gotter AL, Cox CD, Doran SM, Tannenbaum PL, Breslin MJ, Garson SL, Fox SV, Harrell CM, Stevens J, Reiss DR, Cui D, Coleman PJ, Renger JJ (2011) Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist. J Neurogenet 25(1\u20132):52\u201361","journal-title":"J Neurogenet"},{"key":"1403_CR10","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.neuropharm.2011.10.003","volume":"62","author":"CJ Winrow","year":"2011","unstructured":"Winrow CJ, Gotter AL, Cox CD, Tannenbaum PL, Garson SL, Doran SM, Breslin MJ, Schreier JD, Fox SV, Harrell CM, Stevens J, Reiss DR, Cui D, Coleman PJ, Renger JJ (2011) Pharmacological characterization of MK-6096\u2014a dual orexin receptor antagonist for insomnia. Neuropharmacology 62:978\u2013987","journal-title":"Neuropharmacology"},{"issue":"8","key":"1403_CR11","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1177\/0269881111408954","volume":"26","author":"P Bettica","year":"2012","unstructured":"Bettica P, Nucci G, Pyke C, Squassante L, Zamuner S, Ratti E, Gomeni R, Alexander R (2012) Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. J Psychopharmacol 26(8):1058\u20131070","journal-title":"J Psychopharmacol"},{"issue":"4","key":"1403_CR12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.2174\/138920008784220664","volume":"9","author":"SF Zhou","year":"2008","unstructured":"Zhou SF (2008) Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9(4):310\u2013322","journal-title":"Curr Drug Metab"},{"issue":"4","key":"1403_CR13","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/08998280.2000.11927719","volume":"13","author":"CC Ogu","year":"2000","unstructured":"Ogu CC, Maxa JL (2000) Drug interactions due to cytochrome P450. Proc Bayl Univ Med Cent 13(4):421\u2013423","journal-title":"Proc Bayl Univ Med Cent"},{"issue":"7","key":"1403_CR14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2165\/00023210-200317070-00004","volume":"17","author":"LM Hesse","year":"2003","unstructured":"Hesse LM, von Moltke LL, Greenblatt DJ (2003) Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs 17(7):513\u2013532","journal-title":"CNS Drugs"},{"key":"1403_CR15","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) (2012( Draft guidance for industry, drug interaction studies-study design, data analysis, and implications for dosing and labeling. U.S. Department of Health and Human Services, FDA, CDER, CBER, Washington D.C."},{"issue":"10","key":"1403_CR16","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00228-003-0690-3","volume":"59","author":"MM Galteau","year":"2003","unstructured":"Galteau MM, Shamsa F (2003) Urinary 6beta-hydroxycortisol: a validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals. Eur J Clin Pharmacol 59(10):713\u2013733","journal-title":"Eur J Clin Pharmacol"},{"issue":"2","key":"1403_CR17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jchromb.2006.10.018","volume":"847","author":"M Shimizu","year":"2007","unstructured":"Shimizu M, Uno T, Tamura HO, Kanazawa H, Murakami I, Sugawara K, Tateishi T (2007) A developed determination of midazolam and 1\u2032-hydroxymidazolam in plasma by liquid chromatography-mass spectrometry: application of human pharmacokinetic study for measurement of CYP3A activity. J Chromatogr B Analyt Technol Biomed Life Sci 847(2):275\u2013281","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"issue":"3","key":"1403_CR18","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2165\/00003088-200342030-00004","volume":"42","author":"J Dingemanse","year":"2003","unstructured":"Dingemanse J, Schaarschmidt D, van Giersbergen PL (2003) Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet 42(3):293\u2013301","journal-title":"Clin Pharmacokinet"},{"issue":"7","key":"1403_CR19","doi-asserted-by":"crossref","first-page":"587","DOI":"10.2165\/00002018-200831070-00004","volume":"31","author":"E Molden","year":"2008","unstructured":"Molden E, Skovlund E, Braathen P (2008) Risk management of simvastatin or atorvastatin interactions with CYP3A4 inhibitors. Drug Saf 31(7):587\u2013596","journal-title":"Drug Saf"},{"key":"1403_CR20","doi-asserted-by":"crossref","unstructured":"Rowan C, Brinker AD, Nourjah P, Chang J, Mosholder A, Barrett JS, Avigan M (2009) Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors. Pharmacoepidemiol Drug Saf 18(4):301\u2013309","DOI":"10.1002\/pds.1711"},{"issue":"8A","key":"1403_CR21","doi-asserted-by":"crossref","first-page":"27C","DOI":"10.1016\/j.amjcard.2005.12.007","volume":"97","author":"MB Bottorff","year":"2006","unstructured":"Bottorff MB (2006) Statin safety and drug interactions: clinical implications. Am J Cardiol 97(8A):27C\u201331C","journal-title":"Am J Cardiol"},{"issue":"2","key":"1403_CR22","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0090-9556(25)07595-6","volume":"18","author":"S Vickers","year":"1990","unstructured":"Vickers S, Duncan CA, Chen IW, Rosegay A, Duggan DE (1990) Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Drug Metab Dispos 18(2):138\u2013145","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"1403_CR23","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S0090-9556(25)08543-5","volume":"18","author":"S Vickers","year":"1990","unstructured":"Vickers S, Duncan CA, Vyas KP, Kari PH, Arison B, Prakash SR, Ramjit HG, Pitzenberger SM, Stokker G, Duggan DE (1990) In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA reductase. Drug Metab Dispos 18(4):476\u2013483","journal-title":"Drug Metab Dispos"},{"issue":"6","key":"1403_CR24","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.clpt.2006.09.003","volume":"80","author":"PJ Neuvonen","year":"2006","unstructured":"Neuvonen PJ, Niemi M, Backman JT (2006) Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 80(6):565\u2013581","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"1403_CR25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.pharmthera.2006.03.003","volume":"112","author":"Y Shitara","year":"2006","unstructured":"Shitara Y, Sugiyama Y (2006) Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug\u2013drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol Ther 112(1):71\u2013105","journal-title":"Pharmacol Ther"},{"issue":"10","key":"1403_CR26","first-page":"1191","volume":"25","author":"T Prueksaritanont","year":"1997","unstructured":"Prueksaritanont T, Gorham LM, Ma B, Liu L, Yu X, Zhao JJ, Slaughter DE, Arison BH, Vyas KP (1997) In vitro metabolism of simvastatin in humans [SBT] identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 25(10):1191\u20131199","journal-title":"Drug Metab Dispos"},{"issue":"1","key":"1403_CR27","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1046\/j.1365-2125.2003.01833.x","volume":"56","author":"T Prueksaritanont","year":"2003","unstructured":"Prueksaritanont T, Ma B, Yu N (2003) The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br J Clin Pharmacol 56(1):120\u2013124","journal-title":"Br J Clin Pharmacol"},{"key":"1403_CR28","doi-asserted-by":"crossref","unstructured":"Hoever P, de Haas SL, Dorffner G, Chiossi E, van Gerven JM, Dingemanse J (2012) Orexin receptor antagonism: an ascending multiple-dose study with almorexant. J Psychopharmacol 26(8):1071\u20131080","DOI":"10.1177\/0269881112448946"},{"issue":"1","key":"1403_CR29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/0009-9236(95)90068-3","volume":"58","author":"HH Kupferschmidt","year":"1995","unstructured":"Kupferschmidt HH, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 58(1):20\u201328","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"1403_CR30","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1517\/17425255.2011.553189","volume":"7","author":"MJ Hanley","year":"2011","unstructured":"Hanley MJ, Cancalon P, Widmer WW, Greenblatt DJ (2011) The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol 7(3):267\u2013286","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"1","key":"1403_CR31","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2125.2004.02095.x","volume":"58","author":"JJ Lilja","year":"2004","unstructured":"Lilja JJ, Neuvonen M, Neuvonen PJ (2004) Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 58(1):56\u201360","journal-title":"Br J Clin Pharmacol"},{"issue":"5","key":"1403_CR32","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0009-9236(99)70009-3","volume":"66","author":"SM Tsunoda","year":"1999","unstructured":"Tsunoda SM, Velez RL, von Moltke LL, Greenblatt DJ (1999) Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole. Clin Pharmacol Ther 66(5):461\u2013471","journal-title":"Clin Pharmacol Ther"},{"issue":"11","key":"1403_CR33","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1592\/phco.26.11.1601","volume":"26","author":"CW Holtzman","year":"2006","unstructured":"Holtzman CW, Wiggins BS, Spinler SA (2006) Role of P-glycoprotein in statin drug interactions. Pharmacotherapy 26(11):1601\u20131607","journal-title":"Pharmacotherapy"},{"issue":"3","key":"1403_CR34","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/j.1476-5381.2009.00430.x","volume":"158","author":"A Kalliokoski","year":"2009","unstructured":"Kalliokoski A, Niemi M (2009) Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 158(3):693\u2013705","journal-title":"Br J Pharmacol"},{"issue":"4","key":"1403_CR35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1124\/dmd.104.002477","volume":"33","author":"C Chen","year":"2005","unstructured":"Chen C, Mireles RJ, Campbell SD, Lin J, Mills JB, Xu JJ, Smolarek TA (2005) Differential interaction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos 33(4):537\u2013546","journal-title":"Drug Metab Dispos"}],"container-title":["European Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-012-1403-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00228-012-1403-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-012-1403-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T23:46:23Z","timestamp":1744155983000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00228-012-1403-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,19]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["1403"],"URL":"https:\/\/doi.org\/10.1007\/s00228-012-1403-6","relation":{},"ISSN":["0031-6970","1432-1041"],"issn-type":[{"value":"0031-6970","type":"print"},{"value":"1432-1041","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,19]]}}}