Population Pharmacokinetics of an Angiotensin II Receptor Antagonist, Telmisartan, in Healthy Volunteers and Hypertensive Patients

Tatami, Shinji; Sarashina, Akiko; Yamamura, Norio; Igarashi, Takashi

doi:10.2133/dmpk.18.203

Cited by 17 publications

(12 citation statements)

References 11 publications

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“…Patients received medical treatment with telmisartan [9] once daily (40 or 80 mg) and were randomized to either electronic compliance monitoring or standard therapy for 6 months. After 6 months patients were crossed over to the other arm of the study without a washout period.…”

Section: Methodsmentioning

confidence: 99%

“…The initially elevated BP was well controlled in both study groups after half a year, documenting the effectiveness of the study medication. The medication has a long half life [9]. This means that once a patient has reached a steady state of medication in the blood, single forgotten tablets have only a minor influence on plasma levels, and thus the medication has high forgiveness for missed doses.…”

Section: Influence Of the Device On Blood Pressurementioning

confidence: 99%

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The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial

Christensen

Christrup

Fabricius³

et al. 2010

Journal of Hypertension

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The Helping Hand reminder device was most suitable if used for newly diagnosed hypertensive patients, when it improved compliance by 6%. With the present medical treatment, the device does not have any influence on BP control, but with less forgiving medications, the device might make a significant difference. The use of the device can be an easy and effective way to improve compliance in selected patients.

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Section: Methodsmentioning

confidence: 99%

Section: Influence Of the Device On Blood Pressurementioning

confidence: 99%

The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial

Christensen

Christrup

Fabricius³

et al. 2010

Journal of Hypertension

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“…Clearance of an oral dose is related to age, dose, alcohol consumption and hepatic impairment, but not to serum creatinine or smoking history [19] . Telmisartan is not metabolised by the cytochrome P450 system, and hence interactions with other drugs are uncommon.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 92%

Telmisartan in the treatment of hypertension

Rosario

Hendra

2008

Expert Opinion on Drug Metabolism & Toxicology

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Background : Telmisartan is an orally active angiotensin II receptor antagonist prescribed once daily. Objective : To evaluate the efficacy of telmisartan on blood pressure control, and on other end points, when given as monotherapy or in combination. Methods : Review of published literature. Results : Telmisartan produces more effective control of blood pressure over 24 h, especially in the last 6 h of the dosing interval, compared with other antihypertensive agents. It also possesses pleiotrophic effects on lipid and glucose metabolism, but lacks evidence of efficacy in reducing vascular events. Conclusions : Clinical outcome trials expected to report in 2008 will provide hard end points that may demonstrate advantages of telmisartan as monotherapy, or in combination with angiotensin-converting enzyme inhibitors, for managing hypertension.

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“…Each drug was administered once daily for 6 days either alone or in combination in a crossover fashion. Blood samples for concentration measurements were taken before the first dose and the fifth dose and at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3,4,5,6,8,12,16,24,48 and 72 hr after the last dose. Cardiovascular observations consisting of systolic and diastolic blood pressure and HR were measured using digital blood pressure cuffs before dosing from the first to the fifth dose and at 0, 2, 4, 8, 12, 24, 48 and 72 hr after the last dose.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic Model for Blood Pressure and Heart Rate Changes Produced by Telmisartan in Human Beings

Chae

Son

Kim

et al. 2017

Basic Clin Pharma Tox

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Telmisartan, an angiotensin receptor blocker (ARB), 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-invasive markers. Data were acquired from a previous study where telmisartan 80 mg was given once daily for 6 days. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were measured before dosing for days 1-5 and serially after the last dose. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated from SBP and DBP. Relationships between MAP, PP, HR and total peripheral resistance (TPR) were developed. Circadian variation was incorporated into PP and HR, and TPR was assumed to adjust itself in response to changes in PP and HR based on baroreflex mechanism. Drug effects were then described as lowering the set point of MAP through TPR with a physiological feedback effect stimulating HR and PP. Drug concentrations were described by a two-compartment disposition model with first-order absorption and lag time, and first-order elimination. Circadian variation was described by cosine functions, having periods of 12 and 24 hr. A log-linear model was used to describe drug effect, with estimated drug effect parameter of 0.051/hr. Estimated fractional turnover rate of PP, HR and TPR was 11.2 hr. The model successfully described the time courses of these cardiovascular variables. This work demonstrated the feasibility of using non-invasive cardiovascular measurements to derive a mechanistic model for telmisartan in human beings. The model may be suitable for other ARBs.Telmisartan is an antagonist of the angiotensin II type 1 (AT1) receptor that is used for the treatment of hypertension. It selectively inhibits stimulation of the AT1 receptor by angiotensin II. It has a high volume of distribution and is eliminated mainly by the kidneys which results in a long terminal elimination half-life. The compound is not metabolized by cytochrome P450 isoenzymes and has a low risk for P450-based drug interactions [1,2].The action of telmisartan is known to lead to inhibition of aldosterone secretion and reduced vasoconstriction. The time course of its effect involves both rapid and slow responses. The rapid response is mainly due to antagonizing angiotensin II vasoconstriction. The slow response is due to antagonizing angiotensin-mediated aldosterone secretion which leads to a natriuretic effect, followed by decreased plasma volume and consequent decrease in cardiac stroke volume. Both the rapid and slow effects contribute to lowering of blood pressure [1].A population pharmacokinetic (PK) model for telmisartan was first published in 2003 [3] and reported that a two-compartment disposition model with first-order absorption and elimination described the data. A PKPD model of telmisartan has been published [4] in spontaneously hypertensive rats. To the authors' knowledge, no PKPD model of telmisartan has been published in human beings. Previous PKPD models used either an empirical modelli...

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Population Pharmacokinetics of an Angiotensin II Receptor Antagonist, Telmisartan, in Healthy Volunteers and Hypertensive Patients

Abstract: A PPK model for telmisartan developed here well described the individual variability and exposure, and robustness of the model has been validated by the bootstrapping method.

Cited by 17 publications

References 11 publications

The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial

The impact of an electronic monitoring and reminder device on patient compliance with antihypertensive therapy: a randomized controlled trial

Telmisartan in the treatment of hypertension

Mechanistic Model for Blood Pressure and Heart Rate Changes Produced by Telmisartan in Human Beings

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