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Pharmacokinetic & Therapeutic Efficacy of Hydrocholorthiazide with Losartan in Treatment of Hypertension by LC-MS/MS
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| Author:
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GOUTAM MUKHOPADHYAY, SHYMODIP KUNDU, TRIPTI PAL, DEBASMITA MANNA, SAIKAT BHUNIA, PIYAL MAJUMDER, PAYAL JANA, ADITYA SARKAR
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| Abstract:
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Aims & Objectives: The main aim of the present research work is to evaluate the pharmacokinetic parameters as well as therapeutic efficacy of Hydrochlorothiazide along with Losartan used as a fixed dose combined drug in treatment of hypertension.
Methods: This study is carried out by utilizing a typical two periods; randomized & two way complete cross over design. All the volunteers are received fixed dose and single dose product based on the randomization code in each clinical period. Then blood samples are taken and the comperative Pharmacokinetic study was carried out. Matrix effect for internal standard (Letrozole and Candesartan) and analytes (Losartan, LCA & HTCZ) were also carried out as per US-FDA guideline.
Results and Discussion: Maximum plasma concentration of fixed dose combining drug (in which Losartan combined with HCTZ) was found 49±8.87 ng/ml (Cmax) at time 2.75±0.25hrs (tmax) for HCTZ and the average maximum plasma concentration of 6 volunteers was 49.87 ng/ml & Tmax 2.75hrs, AUC0-t was 227.02 ng/ml at 48 hrs and AUC0-a227.67 ng/ml at infinite time & plasma half life (T1/2) of HCTZ 4.91hrs and Ket value is 0.14hr-1. The matrix effect of internal standard (letrozole) ranged between 87.32% to 89.71% and for HCTZ it was between 88.47%-89.86%. And the matrix effect of internal standard (Candesartan) ranged between 93.77%-98.28% & same was found between 95.97%-96.78% in case of Losartan and for LCA it was 95.41%-98.39%.
Conclusion: From the comperative pharmacokinetic study it can be concluded that after fixed dose combined drug treatment the maximum plasma concentration of losartan and losartan carboxylic acid were too much higher than the maximum concentration of losartan and LCA after single drug containing losartan only. And fixed dose combination drug is more susceptible than single dose of Losartan for the treatment of hypertension with better therapeutic efficacy.
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| Keyword:
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Fixed Dose, Pharmacokinetic study, LCA, Hypertension, Cmax, tmax, T1/2
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2020.12.04.027
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| Download:
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