Background: Losartan, one of the more used drugs in Heart Failure (HF) treatment, could modify its bioavailability (BA) by generic formulations and other factors. Hence, the importance of therapeutic drug monitoring.
Objective: Development and validation of a simplified analytical method using HPLC for simultaneous quantification of losartan and E-3174 in human plasma samples. The method was tested for determining the pharmacokinetics parameters of HF patients.
Method: Analytical conditions were optimized using a C18 column (4.6 X 50 mm, 3 µm. Thermo Scientific) at 25ºC. Conditions of mobile phase: a phosphate buffer (0.01M), adjusted to pH 2.5 with phosphoric acid (1M) and Acetonitrile (60:40 v/v). The flow rate was maintained at 1.2 mL/min, on a running time of 5 min and a sample injection volume of 50 µL. Absorbance for measurement of losartan and E-3174 was 200 nm. Pharmacokinetics profiles were determined with Phoenix WinNonlin 8.1 software in a non-compartmental model.
Results: Analytical method developed and validated in this work is precise and accuracy for simultaneous determination of losartan and E-3174 in human plasma samples in a range of 0.02 -10 µg/mL. In HF subjects, lower Tmax and higher Cmax for losartan and E-3174 patent than generic formulation were observed, which can be translated into less biological effect and more time to present it by the generic drug.
Conclusion: The pharmacokinetic profile is dependent on the type of formulation studied (generic/patent) hence the importance of conducting evaluations in our patients to ensure that the expected therapeutic effect is achieved with treatment administered.