What question did this study set out to answer?

To assess whether documented differences in AT1-receptor blockade among different angiotensin receptor antagonists stem primarily from differences in drug dosing.

January 1, 2002Clinical Pharmacology & Therapeutics

Comparative angiotensin II receptor blockade in healthy volunteers: The importance of dosing

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Why the study?

Does valsartan at varying doses improve AT1-receptor blockade compared to losartan, irbesartan, and candesartan in healthy subjects?

Key Points

To assess whether documented differences in AT1-receptor blockade among different angiotensin receptor antagonists stem primarily from differences in drug dosing.
Conducted a randomized, open-label, 3-period crossover study in 24 healthy normotensive volunteers.
Administered once-daily regimens of valsartan (80, 160, and 320 mg), losartan (50 mg), irbesartan (150 mg), and candesartan (8 mg) for 8 days per period.
Evaluated receptor blockade pre-dose and at 4 and 24 hours post-dose on days 1 and 8 using plasma renin activity and an in vitro radioreceptor binding displacement assay.
Valsartan produced dose-dependent AT1-receptor inhibition, with 80 mg valsartan displaying an antagonist profile comparable to 50 mg losartan.
At 4 hours post-dose, both 160 mg and 320 mg valsartan blocked AT1 receptors by 80%, matching the peak blockade of 150 mg irbesartan, though trough blockade at 24 hours was slightly lower.
Based on reactive rises in plasma renin activity on day 8, 160 mg valsartan was equivalent to 150 mg irbesartan and 8 mg candesartan.

Structured PICO

Does valsartan at varying doses improve AT1-receptor blockade compared to losartan, irbesartan, and candesartan in healthy subjects?

Population

24 healthy normotensive subjects

Intervention

Valsartan (80, 160, and 320 mg) once daily for 8 days

Comparator

Losartan 50 mg, irbesartan 150 mg, and candesartan 8 mg once daily for 8 days

Outcome

Angiotensin II AT1-receptor blockade assessed by reactive rise in plasma renin activity and in vitro radioreceptor binding assay before and 4 and 24 hours after drug intake on days 1 and 8surrogate

Differences in AT1 receptor blockade among various ARBs are primarily driven by dosing, with higher doses of valsartan (160-320 mg) achieving comparable blockade to recommended doses of irbesartan and candesartan.

Discussion

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Implication

Equivalence in AT1 blockade supports interchangeable higher-dose valsartan use; confirms dosing as primary driver of ARB differences.

Cite This Study

Maillard et al. (2002) studied this question.

synapsesocial.com/papers/6a8203ae7b220af59de04ed5 https://doi.org/10.1067/mcp.2002.121425

View Full Paper

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Comparative angiotensin II receptor blockade in healthy volunteers: The importance of dosing

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Comparative angiotensin II receptor blockade in healthy volunteers: The importance of dosing

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider