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

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

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.

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.

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.