{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:30:10Z","timestamp":1790044210904,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T00:00:00Z","timestamp":1558915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open\u2010label, three\u2010period, fixed\u2010sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9\u00a0days each. The pharmacokinetics of amlodipine, losartan and EXP\u20103174, an active metabolite of losartan, were assessed at steady\u2010state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady\u2010state (AUC<jats:sub>\u03c4<\/jats:sub>, 165.15\u00a0ng\u00a0h\/mL [amlodipine alone] vs 172.36\u00a0ng\u00a0h\/mL [combination], <jats:italic>P<\/jats:italic>\u00a0=\u00a00.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954\u20101.178)]. In addition, the exposure of EXP\u20103174 was not affected by amlodipine (AUC<jats:sub>\u03c4<\/jats:sub>, 1159.46\u00a0ng\u00a0h\/mL vs 1105.10\u00a0ng\u00a0h\/mL, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.295) (GMR [90% CI], 0.957 [0.891\u20101.027]). However, amlodipine significantly decreased the exposure of losartan at steady\u2010state (AUC<jats:sub>\u03c4<\/jats:sub>, 1241.50\u00a0ng\u00a0h\/mL vs 1082.02\u00a0ng\u00a0h\/mL, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.006) (GMR [90% CI], 0.875 [0.813\u20100.942]) and increased oral clearance of losartan (84.65\u00a0L\/h vs 97.26\u00a0L\/h, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co\u2010administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.<\/jats:p>","DOI":"10.1111\/bcpt.13244","type":"journal-article","created":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T21:17:54Z","timestamp":1557177474000},"page":"345-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings"],"prefix":"10.1111","volume":"125","author":[{"given":"Jin\u2010Woo","family":"Park","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Korea University College of Medicine Korea University Anam Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung\u2010Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Korea University College of Medicine Korea University Anam Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Il Kim","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center Hanmi Pharm. 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