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International Journal of Pharmacology
  Year: 2016 | Volume: 12 | Issue: 2 | Page No.: 101-107
DOI: 10.3923/ijp.2016.101.107
 
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Evaluation of the Possible Pharmacokinetic Interaction Between Amlodipine, Losartan and Hydrochlorothiazide in Mexican Healthy Volunteers

Noemi Santos-Caballero, Lina Marcela Barranco-Garduno, Jose Carlos Aguilar-Carrasco, Miriam del Carmen Carrasco-Portugal and Francisco Javier Flores-Murrieta

Abstract:
The fixed-dose combinations of drugs are alternatives for a major control of chronical diseases such hypertension. Amlodipine, losartan and hydrochlorothiazide are widely used as pharmacological treatment of this cardiovascular disorder. Since these drugs have different mechanism of action, it could be assumed that a fixed-dose combination containing them will provide therapeutic advantages and greater adherence to the treatment. However, firstly is necessary to verify a possible pharmacokinetic interaction between the components. In this study, the oral pharmacokinetics of amlodipine, losartan and hydrochlorothiazide in a fixed-dose combination formulation were evaluated and compared against the individual components in 26 healthy volunteers. After an overnight fast subjects received an oral dose of losartan (50 mg), hydrochlorothiazide (12.5 mg), amlodipine (5 mg) or the same doses in fixed-dose combination formulation in four periods according to a randomized crossover design. Blood samples were obtained at selected times for a period of 72 h. Plasma was obtained and stored frozen at -80°C until analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry. The treatments were well tolerated. No changes were observed in the pharmacokinetic parameters of amlodipine. For losartan and losartan acid the plasma levels were slightly higher whereas for hydrochlorothiazide greatly increase more than twice their plasma levels with fixed-dose combination formulation. These results suggest pharmacokinetic interactions between these compounds. Further studies are necessary in order to establish the mechanisms of these interactions, however, clinical relevance should be evaluated in clinical studies in patients in which this fixed-dose combination formulation could be a therapeutic alternative.
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How to cite this article:

Noemi Santos-Caballero, Lina Marcela Barranco-Garduno, Jose Carlos Aguilar-Carrasco, Miriam del Carmen Carrasco-Portugal and Francisco Javier Flores-Murrieta, 2016. Evaluation of the Possible Pharmacokinetic Interaction Between Amlodipine, Losartan and Hydrochlorothiazide in Mexican Healthy Volunteers. International Journal of Pharmacology, 12: 101-107.

DOI: 10.3923/ijp.2016.101.107

URL: https://scialert.net/abstract/?doi=ijp.2016.101.107

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