{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:18:13Z","timestamp":1788272293133,"version":"build-2803163510"},"reference-count":81,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[1996,6,1]],"date-time":"1996-06-01T00:00:00Z","timestamp":833587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[1996,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To describe a new class of antihypertensive agents, the angiotensin II receptor antagonists, with emphasis on the prototype losartan. Pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, and dosing guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>A MEDLINE search of English-language literature published from 1966 through 1995 was performed. In addition, Merck and Co. provided bibliographic data on file for losartan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Emphasis was placed on clinical and pharmacokinetic studies in humans. Controlled, double-blind studies were evaluated to assess the efficacy and adverse effect profile of losartan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis<\/jats:title>\n                    <jats:p>Losartan is a nonpeptide, competitive antagonist of the type 1 angiotensin II receptor. In comparative clinical trials, losartan appears to have antihypertensive efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitors. Losartan is well tolerated, with an adverse effect profile similar to that of placebo and a reduced incidence of cough versus that with ACE inhibitors. A combination product consisting of losartan 50 mg and hydrochlorothiazide 12.5 mg has also received approval for the treatment of hypertension. The combination product is not indicated for initial therapy, but is recommended for patients who do not respond adequately to losartan monotherapy. The angiotensin II receptor antagonists are also being investigated for beneficial effects in patients with ventricular hypertrophy, renal disease, and heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Losartan, the first angiotensin II receptor antagonist to receive approval for use in the US, appears to be an effective new antihypertensive agent with an adverse effect profile similar to that of placebo. Losartan may be an alternative for patients who cannot tolerate ACE inhibitors. However, the effect of losartan on mortality remains to be evaluated. The role of the angiotensin II receptor antagonists in areas such as ventricular hypertrophy, renal function, and heart failure has yet to be determined.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/106002809603000611","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T20:02:48Z","timestamp":1500408168000},"page":"625-636","source":"Crossref","is-referenced-by-count":23,"title":["Angiotensin II Receptor Antagonists: The Prototype Losartan"],"prefix":"10.1177","volume":"30","author":[{"given":"Karen L","family":"Schaefer","sequence":"first","affiliation":[{"name":"Kaiser Permanente, Colorado Region, 4803 Ward Rd, Wheat Ridge, CO 80033, FAX 303\/421-6036"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Porter","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Colorado Region"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda R","family":"Morand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rudis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[1996,6]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.","author":"National Institutes of Health.","year":"1993","unstructured":"National Institutes of Health. The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.NIH publication No. 93-1088. Bethesda, MD: National Institutes of Health, January 1993."},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1993.00410020042003"},{"key":"e_1_2_1_4_2","first-page":"1","volume-title":"Clinical hypertension.","author":"Kaplan NM","year":"1994","unstructured":"Kaplan NM. Clinical hypertension. 6th ed. Baltimore: Williams and Wilkins, 1994: 1\u20139.","edition":"6"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"I-113","DOI":"10.1161\/01.HYP.13.5_Suppl.I113","article-title":"Antihypertensive drug use: trends in the United States from 1973 to 1985.","volume":"13","author":"Gross TP","year":"1989","unstructured":"Gross TP, Wise RP, Knapp DE. Antihypertensive drug use: trends in the United States from 1973 to 1985. Hypertension 1989; 13(suppl I): I-113\u20138.","journal-title":"Hypertension"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1995.00430080067009"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199000392-00002"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(87)90013-7"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1993.tb01939.x"},{"issue":"4","key":"e_1_2_1_10_2","first-page":"51","article-title":"Molecular mechanism of renin release.","volume":"16","author":"Kurtz A","year":"1990","unstructured":"Kurtz A, Scholz H, Della-Bruna R. Molecular mechanism of renin release. J Cardiovasc Pharmacol 1990; 16(suppl 4): 51\u20137.","journal-title":"J Cardiovasc Pharmacol"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199447040-00003"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/5.12.221S"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(94)90061-2"},{"key":"e_1_2_1_14_2","first-page":"I4","article-title":"Circulating versus local renin-angiotensin system in cardiovascular homeostasis.","volume":"77","author":"Dzau VJ","year":"1988","unstructured":"Dzau VJ. Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 1988; 77(suppl I): I4\u201313.","journal-title":"Circulation"},{"issue":"1","key":"e_1_2_1_15_2","first-page":"1","article-title":"Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart.","volume":"88","author":"Dzau VJ","year":"1993","unstructured":"Dzau VJ. Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart. Basic Res Cardiol 1993; 88(suppl 1): 1\u201314.","journal-title":"Basic Res Cardiol"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1993.00410080011002"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199400474-00003"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1994.tb04000.x"},{"key":"e_1_2_1_19_2","first-page":"260","article-title":"Discovery of remikiren as the first orally active renin inhibitor.","volume":"43","author":"Clozel JP","year":"1993","unstructured":"Clozel JP, Fischli W. Discovery of remikiren as the first orally active renin inhibitor. Drug Res 1993; 43: 260\u20132.","journal-title":"Drug Res"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04070.x"},{"key":"e_1_2_1_21_2","first-page":"236","article-title":"Prostaglandin-mediated actions of the renin-angiotensin system.","volume":"43","author":"Schror K","year":"1993","unstructured":"Schror K. Prostaglandin-mediated actions of the renin-angiotensin system. Drug Res 1993; 43: 236\u201340.","journal-title":"Drug Res"},{"issue":"10","key":"e_1_2_1_22_2","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1097\/00005344-199200209-00003","article-title":"Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology.","volume":"20","author":"Skidgel RA","year":"1992","unstructured":"Skidgel RA. Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. J Cardiovasc Pharmacol 1992; 20(suppl 10): S4\u20139.","journal-title":"J Cardiovasc Pharmacol"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1994.tb01989.x"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-3-234"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1989.tb04107.x"},{"issue":"10","key":"e_1_2_1_26_2","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1097\/00005344-199200209-00006","article-title":"Effect of bradykinin on arteries and veins in systemic and pulmonary circulation.","volume":"20","author":"Bonner G","year":"1992","unstructured":"Bonner G. Effect of bradykinin on arteries and veins in systemic and pulmonary circulation. J Cardiovasc Pharmacol 1992; 20(suppl 10): S21\u20137.","journal-title":"J Cardiovasc Pharmacol"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.304.6832.941"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03410070095035"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199302000-00015"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.29.6.664"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90498-H"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/5.12.209S"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)10725-8"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00098a018"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.1.22"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)11212-3"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(92)90627-2"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb13425.x"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90144-S"},{"key":"e_1_2_1_40_2","first-page":"1077","article-title":"In vitro pharmacology of a nonpeptide angiotensin II receptor antagonist, SC-51316.","volume":"42","author":"Olins GM","year":"1992","unstructured":"Olins GM, Corpus VM, McMahon EG, Palomo MA, Schuh JF, Blehm DJ, et al. In vitro pharmacology of a nonpeptide angiotensin II receptor antagonist, SC-51316. J Pharmacol Exp Ther 1992; 42: 1077\u201382.","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"e_1_2_1_41_2","first-page":"S19","article-title":"Discovery of losartan, the first specific non-peptide angiotensin II receptor antagonist.","volume":"11","author":"Siegl PKS","year":"1993","unstructured":"Siegl PKS. Discovery of losartan, the first specific non-peptide angiotensin II receptor antagonist. J Hypertens 1993; 11(suppl 3): S19\u201322.","journal-title":"J Hypertens"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)19981-3"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.17.4.480"},{"key":"e_1_2_1_44_2","volume-title":"Cozaar (losartan potassium).","author":"Package insert.","year":"1995","unstructured":"Package insert. Cozaar (losartan potassium). West Point, PA: Merck and Co., Inc., April 1995."},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.56"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.4.1333"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.21.5.704"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199409000-00011"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.1.37"},{"key":"e_1_2_1_50_2","unstructured":"FDC reports. The pink sheet. April 17 1995: 22."},{"key":"e_1_2_1_51_2","unstructured":"FDC reports. The pink sheet. May 8 1995: 4\u20135."},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1993.tb05696.x"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90593-S"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/5.12.247S"},{"key":"e_1_2_1_55_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1995.00430040081010"},{"key":"e_1_2_1_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/6.1.28"},{"key":"e_1_2_1_57_2","first-page":"19A","article-title":"Efficacy and safety of losartan in patients with essential hypertension (abstract).","volume":"5","author":"Nelson E","year":"1992","unstructured":"Nelson E, Arcuri K, Ikeda L, Snavely D, Sweet C. Efficacy and safety of losartan in patients with essential hypertension (abstract). Am J Hypertens 1992; 5: 19A.","journal-title":"Am J Hypertens"},{"key":"e_1_2_1_58_2","first-page":"D2","article-title":"Antihypertensive efficacy and tolerability of losartan compared to atenolol in patients with mild to moderate essential hypertension (abstract).","volume":"7","author":"Keller SE","year":"1994","unstructured":"Keller SE, Makris L, Nelson EB, Sweet CS. Antihypertensive efficacy and tolerability of losartan compared to atenolol in patients with mild to moderate essential hypertension (abstract). Am J Hypertens 1994; 7: D2.","journal-title":"Am J Hypertens"},{"issue":"4","key":"e_1_2_1_59_2","first-page":"42A","article-title":"Antihypertensive effect of the combination therapy with losartan and hydrochlorothiazide in mild to severely hypertensive patients who are not adequately controlled on HCTZ alone (abstract).","volume":"7","author":"Soffer BA","year":"1994","unstructured":"Soffer BA, Wright JT, Pratt JH, Wiens B, Dai CX, Turpin J, et al. Antihypertensive effect of the combination therapy with losartan and hydrochlorothiazide in mild to severely hypertensive patients who are not adequately controlled on HCTZ alone (abstract). Am J Hypertens 1994; 7(4): 42A.","journal-title":"Am J Hypertens"},{"issue":"4","key":"e_1_2_1_60_2","first-page":"37A","article-title":"Efficacy and safety of losartan combined with hydrochlorothiazide in patients with mild to severe hypertension (abstract).","volume":"7","author":"Simpson RL","year":"1994","unstructured":"Simpson RL, Morlin C, Toh C, Snavely DB, Nelson EB, Goldberg AI. Efficacy and safety of losartan combined with hydrochlorothiazide in patients with mild to severe hypertension (abstract). Am J Hypertens 1994; 7(4): 37A.","journal-title":"Am J Hypertens"},{"key":"e_1_2_1_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb16936.x"},{"key":"e_1_2_1_62_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.51.030189.001201"},{"key":"e_1_2_1_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(92)90589-H"},{"key":"e_1_2_1_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/4.4.327S"},{"key":"e_1_2_1_65_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199301000-00006"},{"issue":"2","key":"e_1_2_1_66_2","first-page":"S37","article-title":"Effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease.","volume":"12","author":"Gansevoort RT","year":"1994","unstructured":"Gansevoort RT, de Zeeuw D, Shahinfar S, Redfield A, de Jong PE. Effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease. J Hypertens 1994; 12(suppl 2): S37\u201342.","journal-title":"J Hypertens"},{"key":"e_1_2_1_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(81)90739-0"},{"key":"e_1_2_1_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5273(86)90197-X"},{"key":"e_1_2_1_69_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_2_1_70_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_2_1_71_2","first-page":"H833","article-title":"Chronic captopril and losartan (DuP 753) administration in rats with high-output heart failure.","volume":"263","author":"Qing G","year":"1992","unstructured":"Qing G, Garcia R. Chronic captopril and losartan (DuP 753) administration in rats with high-output heart failure. Am J Physiol 1992; 263: H833\u201340.","journal-title":"Am J Physiol"},{"key":"e_1_2_1_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/4.4.334S"},{"key":"e_1_2_1_73_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.3.691"},{"key":"e_1_2_1_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80413-5"},{"key":"e_1_2_1_75_2","first-page":"A8","article-title":"The incidence of cough with the angiotensin II receptor antagonist, losartan, is significantly less than with angiotensin-converting enzyme inhibitors and is similar to that of placebo (abstract).","volume":"7","author":"Faison EP","year":"1994","unstructured":"Faison EP, Snavely DB, Thiyagarajan B, Nelson EB. The incidence of cough with the angiotensin II receptor antagonist, losartan, is significantly less than with angiotensin-converting enzyme inhibitors and is similar to that of placebo (abstract). Am J Hypertens 1994; 7: A8.","journal-title":"Am J Hypertens"},{"key":"e_1_2_1_76_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512073332316"},{"key":"e_1_2_1_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00266358"},{"key":"e_1_2_1_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/7.12.1041"},{"key":"e_1_2_1_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04018.x"},{"key":"e_1_2_1_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04097.x"},{"key":"e_1_2_1_81_2","first-page":"160","article-title":"Pharmacokinetics of losartan (MK-954 or DuP 753) in patients with renal insufficiency (abstract).","volume":"53","author":"Lo MW","year":"1993","unstructured":"Lo MW, Shahinfar S, Furtek CI, Ritter M, Shaw WC, Gehr T, et al. Pharmacokinetics of losartan (MK-954 or DuP 753) in patients with renal insufficiency (abstract). Clin Pharmacol Ther 1993; 53: 160.","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_1_82_2","first-page":"140","article-title":"Safety and antihypertensive effects of losartan (MK-954; DuP 753), a new angiotensin II receptor antagonist, in patients with hypertension and renal disease (abstract).","volume":"53","author":"Shaw W","year":"1993","unstructured":"Shaw W, Keane W, Sica D, Halstenson C, Gehr T, Marshall C. Safety and antihypertensive effects of losartan (MK-954; DuP 753), a new angiotensin II receptor antagonist, in patients with hypertension and renal disease (abstract). Clin Pharmacol Ther 1993; 53: 140.","journal-title":"Clin Pharmacol Ther"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/106002809603000611","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/106002809603000611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:04:50Z","timestamp":1777374290000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/106002809603000611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,6]]},"references-count":81,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1996,6]]}},"alternative-id":["10.1177\/106002809603000611"],"URL":"https:\/\/doi.org\/10.1177\/106002809603000611","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,6]]}}}