{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:58:49Z","timestamp":1790953129731,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:00:00Z","timestamp":1504656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Abstract<\/jats:title>Telmisartan, an angiotensin receptor blocker (ARB<\/jats:styled-content>), is indicated for the treatment of essential hypertension. This study aimed to develop a mechanistic model of telmisartan drug effect in human beings using non\u2010invasive markers. Data were acquired from a previous study where telmisartan 80\u00a0mg was given once daily for 6\u00a0days. Systolic (SBP<\/jats:styled-content>) and diastolic blood pressure (DBP<\/jats:styled-content>) and heart rate (HR<\/jats:styled-content>) were measured before dosing for days 1\u20135 and serially after the last dose. Mean arterial pressure (MAP<\/jats:styled-content>) and pulse pressure (PP<\/jats:styled-content>) were calculated from SBP<\/jats:styled-content> and DBP<\/jats:styled-content>. Relationships between MAP<\/jats:styled-content>, PP<\/jats:styled-content>, HR<\/jats:styled-content> and total peripheral resistance (TPR<\/jats:styled-content>) were developed. Circadian variation was incorporated into PP<\/jats:styled-content> and HR<\/jats:styled-content>, and TPR<\/jats:styled-content> was assumed to adjust itself in response to changes in PP<\/jats:styled-content> and HR<\/jats:styled-content> based on baroreflex mechanism. Drug effects were then described as lowering the set point of MAP<\/jats:styled-content> through TPR<\/jats:styled-content> with a physiological feedback effect stimulating HR<\/jats:styled-content> and PP<\/jats:styled-content>. Drug concentrations were described by a two\u2010compartment disposition model with first\u2010order absorption and lag time, and first\u2010order elimination. Circadian variation was described by cosine functions, having periods of 12 and 24\u00a0hr. A log\u2010linear model was used to describe drug effect, with estimated drug effect parameter of 0.051\/hr. Estimated fractional turnover rate of PP<\/jats:styled-content>, HR<\/jats:styled-content> and TPR<\/jats:styled-content> was 11.2\u00a0hr. The model successfully described the time courses of these cardiovascular variables. This work demonstrated the feasibility of using non\u2010invasive cardiovascular measurements to derive a mechanistic model for telmisartan in human beings. The model may be suitable for other ARB<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1111\/bcpt.12856","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T09:23:00Z","timestamp":1502702580000},"page":"139-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanistic Model for Blood Pressure and Heart Rate Changes Produced by Telmisartan in Human Beings"],"prefix":"10.1111","volume":"122","author":[{"given":"Dongwoo","family":"Chae","sequence":"first","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul Korea"},{"name":"Brain Korea 21 Plus Project for Medical Science Yonsei University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mijeong","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine Seoul Korea"},{"name":"Brain Korea 21 Plus 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