Chronopharmacology of Valsartan in Normotensive Subjects

Study Overview
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Brief Summary
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The choice of drug administration time may affect the pharmacokinetics and/or drug response, and knowledge of any such circadian rhythm-dependent effects may help to reduce side effects or to enhance efficacy. This study designed to investigate the potential influence of the time of drug administration on the pharmacokinetics and pharmacodynamics of the valsartan in healthy subjects.

Detailed Description
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International guidelines recommend the use of long acting, once-daily medications that provide 24h efficacy; they improve adherence to therapy and minimize BP variability with smoother and more consistent BP control. Valsartan has been approved to be used once-daily, without any specification of treatment-time in package insert. Several trials have investigated the differential effects of morning versus evening administration of valsartan in hypertensive patients, however, the results of these studies were contradicting. Furthermore, the specific administration time dependent dose response curve have not been previously investigated. So, this study designed to investigate the potential influence of the time of drug administration on the pharmacokinetics and pharmacodynamics of the valsartan in healthy subjects.

Official Title
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A Comparative Pharmacokinetic and Pharmacodynamic Study of Morning Versus Evening Administration of Valsartan in Healthy Adults

Conditions
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Healthy Normotensive Volunteers

Intervention / Treatment
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* Drug: Valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old and not more than 45 healthy male volunteers Actual weight no more than ± 30% from ideal body weight based on sex, height, and body frame Who had passed all the screening parameters including physical examination, laboratory tests. Who had to be able to communicate effectively with study personnel, be literate, and able to give consent. diurnal active subjects with eight hour night sleep. free of any drug exposure known to interfere with the pharmacokinetics/pharmacodynamics or assay of valsartan for at least 10 days prior to the study Exclusion Criteria: Treatment with any known enzyme-inducing/inhibiting agents within 30 days prior to the start of the study and throughout the study. Susceptibility to allergic reactions to valsartan. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption. Gastrointestinal diseases. Renal diseases. Cardiovascular diseases. Pancreatic disease including diabetes. Hepatic diseases. Hematological disease or pulmonary disease Abnormal laboratory values. Subjects who have donated blood or who have been involved in multiple dosing study requiring a large volume of blood (more than 500 ml) to be drawn within 6 weeks preceding the start of the study. Nocturnal active subjects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Other: morning administration<br>administration of single oral dose valsartan (160 mg) in the morning | Drug: Valsartan<br>* single oral dose of 160 mg valsartan under fasting conditions<br>* Other names: Diovan;|
| Other: evening administration<br>administration of single oral dose valsartan (160 mg) in the evening | Drug: Valsartan<br>* single oral dose of 160 mg valsartan under fasting conditions<br>* Other names: Diovan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters | Maximum plasma concentration (Cmax), | blood samples will be collected for 48 hour after drug administration | 
| Pharmacokinetic parameters | Area under the curve (AUC). | blood samples will be collected for 48 hour after drug administration | 
| Pharmacokinetic parameters | elimination half life (T1/2) | blood samples will be collected for 48 hour after drug administration | 
| pharmacodynamic parameter | systolic blood pressure (mm Hg) ,diastolic blood pressure (mm Hg) | Blood samples will be measured at prespecified time points for 48 hour after drug administration | 
| pharmacodynamic parameter | Heart rate (beat/min) | Blood samples will be measured at prespecified time points for 48 hour after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronokinetics, chronodynamics, chronopharmacology, valsartan