What is the clinical evidence from this study?

Study design: Other. Intervention: Irbesartan vs. Losartan or vehicle. Primary outcome: Inhibition of AT(1) receptor binding in the rat kidney.

What question did this study set out to answer?

To compare the in vivo and in vitro inhibitory effects of oral irbesartan and losartan on renal AT1 angiotensin II receptors in rats.

September 15, 2000Clinical Science

Comparative in vivo effects of irbesartan and losartan on angiotensin II receptor binding in the rat kidney following oral administration

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Key result

Oral irbesartan and losartan effectively inhibit rat kidney AT1 receptors, though irbesartan appears less potent.

Population

Male Sprague-Dawley rats (250-300 g)

Comparison

Irbesartan oral gavage at doses of 1, 3, 10, 30… vs Losartan oral gavage at doses of 1, 3, 10, 30 or…

Design

Preclinical

Follow-up

24 hours

Authors

MFMaurice E. FabianiThe University of Melbourne DDDiem DinhInterventional Cardiology LNL. NassisThe University of Melbourne

Discussion

Member takes

Implication

Rat data on AT1 inhibition do not guide ARB dosing; leaves open translation to human renal disease.

Key Points

To compare the in vivo and in vitro inhibitory effects of oral irbesartan and losartan on renal AT1 angiotensin II receptors in rats.
Male Sprague-Dawley rats were orally gavaged with irbesartan or losartan at doses of 1, 3, 10, 30, or 100 mg/kg or vehicle control.
Kidneys and blood were harvested at 0, 1, 2, 8, or 24 hours post-administration to quantify receptor binding via in vitro autoradiography using (125)I-[Sar(1),Ile(8)]angiotensin II.
Both irbesartan (1–100 mg/kg) and losartan (1–30 mg/kg) caused dose-dependent inhibition of renal AT1 receptors at 1 hour, with maximal inhibition at 100 mg/kg and 30 mg/kg, respectively, and maintained tissue blockade at 24 hours.
At a 10 mg/kg dose, maximal inhibition occurred at 1–2 hours for losartan and 2–8 hours for irbesartan.
In vitro displacement yielded IC50 values of 1.00 ± 0.2 nM for irbesartan, 3.5 ± 0.4 nM for EXP3174, and 8.9 ± 1.1 nM for losartan, showing higher in vitro affinity for irbesartan despite lower in vivo dose-potency.

Structured PICO

Population

Male Sprague-Dawley rats (250-300 g) evaluated for AT1 receptor binding in the kidney following oral administration of irbesartan or losartan.

Intervention

Irbesartan oral gavage at doses of 1, 3, 10, 30 or 100 mg/kg

Comparator

Losartan oral gavage at doses of 1, 3, 10, 30 or 100 mg/kg, or corresponding vehicle

Outcome

Inhibition of AT(1) receptor binding in the rat kidney determined by quantitative in vitro autoradiographysurrogate

Irbesartan and losartan produce effective and sustained inhibition of AT(1) receptors in vivo in the rat kidney, though irbesartan has a slower onset of action despite higher in vitro affinity.

Cite This Study

Fabiani et al. (2000) studied this question. Irbesartan vs. Losartan or vehicle was evaluated on Inhibition of AT(1) receptor binding in the rat kidney. Oral administration of irbesartan and losartan produced effective and sustained dose-dependent inhibition of AT(1) receptors in the rat kidney, though irbesartan appeared less potent in vivo.

synapsesocial.com/papers/6aa2252b1c302ea162b2b076 https://doi.org/10.1042/cs0990331

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Comparative in vivo effects of irbesartan and losartan on angiotensin II receptor binding in the rat kidney following oral administration

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Comparative in vivo effects of irbesartan and losartan on angiotensin II receptor binding in the rat kidney following oral administration

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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