Effects of Sodium Intake on (PK/PD) Relationship of a Single Dose of a Renin Angiotensin System-Blocker

Study Overview
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Brief Summary
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The impact of sodium intake on plasma drug concentrations has previously been reported in the literature for verapamil and quinidine but, to the investigators' knowledge, never with renin-angiotensin system blockers such as AT1R antagonists and angiotensin converting enzyme inhibitors.

Detailed Description
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The impact of sodium intake on plasma drug concentrations concentrations obtained after a single oral dose of RAS blocking drugs (ramipril 10 mg, valsartan 160 mg, candesartan 8 mg) or a blocker as control (ATENOLOL 50 mg) will be compared in healthy normotensive men randomly assigned to a 6-day replated-sodium diet or a sodium depletion.

Official Title
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Effects of Sodium Intake on Pharmacokinetic/Pharmacodynamic Relationship of a Single Dose of a Renin Angiotensin System-Blocker, or a Beta-Blocker in Normotensive Sodium-Depleted or Replated Volunteers in a Cross-Over Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: high sodium diet
* Drug: low sodium diet
* Drug: ramipril 10 mg
* Drug: valsartan 160 mg
* Drug: candesartan 8 mg
* Drug: atenolol 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 64 (16 per treatment goup) non-smoking healthy male volunteers Aged between 18 and 35 years after a complete clinical examination Safety laboratory measurements Having given written informed consent. Exclusion Criteria: hypertension known disease diabetes mellitus known hypersensitivity contraindication to ACE inhibitors history of cardiac or pulmonary disease or asthma conditions which do not permit medical follow-up and compliance with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>treatment | Drug: high sodium diet<br>* high sodium diet<br>Drug: low sodium diet<br>* low sodium diet<br>Drug: ramipril 10 mg<br>* ramipril 10 mg<br>Drug: valsartan 160 mg<br>* valsartan 160 mg<br>Drug: candesartan 8 mg<br>* candesartan 8 mg<br>Drug: atenolol 50 mg<br>* atenolol 50 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) up to the 48 hour time point of plasma drug concentrations between a replated-sodium diet and sodium depletion |  | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High sodium diet, Low sodium diet, Renin-angiotensin system blockers, AT1 receptor (AT1R) antagonist, ACE inhibition