Evaluation of the possible pharmacokinetic interaction between amlodipine, losartan and hydrochlorothiazide in Mexican healthy volunteers

The fixed-dose combinations of drugs are alternatives for a major control of chronical diseases such hypertension. Amlodipine, losartanand hydrochlorothiazide are widely used as pharmacological treatment of this cardiovascular disorder. Since these drugs have differentmechanism of action, it could be assumed that a fixed-dose combination containing them will provide therapeutic advantages and greateradherence to the treatment. However, firstly is necessary to verify a possible pharmacokinetic interaction between the components. Inthis study, the oral pharmacokinetics of amlodipine, losartan and hydrochlorothiazide in a fixed-dose combination formulation wereevaluated and compared against the individual components in 26 healthy volunteers. After an overnight fast subjects received an oraldose of losartan (50 mg), hydrochlorothiazide (12.5 mg), amlodipine (5 mg) or the same doses in fixed-dose combination formulationin four periods according to a randomized crossover design. Blood samples were obtained at selected times for a period of 72 h. Plasmawas obtained and stored frozen at -80EC until analyzed by ultra performance liquid chromatography coupled with tandem massspectrometry. The treatments were well tolerated. No changes were observed in the pharmacokinetic parameters of amlodipine. Forlosartan and losartan acid the plasma levels were slightly higher whereas for hydrochlorothiazide greatly increase more than twice theirplasma 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 evaluatedin clinical studies in patients in which this fixed-dose combination formulation could be a therapeutic alternative.