Pharmacokinetic Interactions of Valsartan and Hydrochlorothiazide

Study Overview
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Brief Summary
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This study was conducted to compare the rate and extent of absorption of valsartan and hydrochlorothiazide following oral administration as a fixed dose combination tablet and concomitant administration of the individual drugs under fasting conditions in healthy Egyptian subjects. The study was extended to investigate any potential reaction between VAL and HCT.

Detailed Description
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This study comprised 2 separate parts, I and II; each was a single-dose, open-label, 4-crossover periods separated by a 2 weeks washout, and 4-Treatments. Part I consisted of Treatments A (VAL 160 mg alone), B (HCT 12.5 mg alone), C (VAL 160 mg + HCT 12.5 mg) and D (VAL / HCT 160 mg/12.5mg) and Part II consisted of Treatments E (VAL 320 mg alone), F (HCT 25 mg alone), G (VAL 320 mg + HCT 25 mg) and H (VAL / HCT 320 mg/25 mg). Blood samples were collected up to 48 hours postdose and plasma was analyzed for VAL and HCT concentrations using HPLC. The pharmacokinetic properties of each drug after co-administration of VAL and HCT were compared with those of each drug administered alone.

Official Title
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Pharmacokinetic Interactions of Valsartan and Hydrochlorothiazide: An Open-Label, Randomized, Four-Period Crossover Study in Healthy Egyptian Male Volunteers

Conditions
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Healthy Normotensive Participants

Intervention / Treatment
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* Drug: Valsartan/Hydrochlorothiazide
* Drug: Valsartan
* Drug: Hydrochlorothiazide


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 Free of any drug exposure known to interfere with the pharmacokinetics or assay of fexofenadine for at least 10 days prior to the study Who had to be able to communicate effectively with study personnel, be literate, and able to give consent. Exclusion Criteria: A clinically significant abnormal physical exam, medical history, or laboratory studies If they showed a sitting SBP of >140 or <100 mmHg, DBP > 90 or <60mm Hg, or a pulse rate of > 95 or < 50 beats/min at screening A history of serious intolerance, allergy, or sensitivity to fexofenadine The use of any prescription drug within the previous month or use of any over-the-counter medication (with the exception of acetaminophen) within the past 14 days A history of blood dyscrasias A history of alcohol or drug abuse within the past year Donation of blood during the 8 weeks prior to the study or plans to donate blood during or within 8 weeks of completing the study Unable to tolerate vein puncture and multiple blood samplings Any surgical/medical condition that might alter drug absorption, distribution, metabolism, or excretion Cannot follow instructions, in the opinion of the investigator.

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Valsartan 160 mg alone<br>Valsartan alone | Drug: Valsartan<br>* Valsartan alone<br>|
| Other: Hydrochlorothiazide 12.5 mg alone<br>Hydrochlorothiazide alone | Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide alone<br>|
| Other: Valsartan160 mg + Hydrochlorothiazide12.5 mg<br>Concomitant administration of valsartan 160 mg + Hydrochlorothiazide 12.5 mg | Drug: Valsartan/Hydrochlorothiazide<br>* Co-administration or fixed dose combination<br>* Other names: Pharmacokinetic interaction;|
| Other: Valsartan / Hydrochlorothiazide 160 mg/12.5mg<br>Fixed dose combination of valsartan 160 mg + Hydrochlorothiazide 12.5 mg | Drug: Valsartan/Hydrochlorothiazide<br>* Co-administration or fixed dose combination<br>* Other names: Pharmacokinetic interaction;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability | Tolerability was assessed based on changes in vital signs (temperature, blood pressure, pulse, and heart rate), measured before dosing in each period and approximately every 4 hours thereafter, and laboratory tests (hematology, biochemistry, liver function, and urinalysis), and performed at baseline and at the end of the study. In addition, a physician questioned volunteers about any adverse events occurring during the study, addressed them as necessary, and recorded them on the appropriate form. This physician was not blinded to treatment, but had no involvement in the study. | Participants will be followed for the duration of study, an expected average of 6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fixed dose combination, Pharmacokinetics, Valsartan, Hydrochlorothiazide