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Latika Budhalakoti , Suneela S. Dhaneshwar* , Shakuntala Chopade, Hemant Kamble, and S. L. Bodhankar


Recent WHO guidelines recommend combination antihypertensive therapy as the first-line therapy for hypertension because monotherapies are often abortive and may lead to delayed BP control, increased risk of stroke and death. Present work was focused on designing a thioester- linked mutual prodrug of captopril and furosemide as a combination therapy. The main objectives were to extend duration of action of furosemide, conserve normal potassium levels in body, minimize thiol- induced side effects of captopril, lower the gastric irritant effect of furosemide and achieve synergistic antihypertensive effect. The thioester prodrug FC was synthesized and characterized by spectral analysis. In vitro release was studied by HPTLC. It was screened for diuretic and antihypertensive effects in experimental models in Wistar rats. In the small intestinal homogenates, 95% hydrolysis of FC was observed at the end of 7h. FC showed many promising features like prolonged duration of diuretic activity, synergistic antihypertensive activity, conservation of potassium loss, decrease in thiol- induced skin rashes and absence of cardiotoxicity. We concluded that the mutual prodrug exhibited improved delivery properties and efficacy compared to monotherapy or co-administration of captopril and furosemide in the form of a physical mixture.

Keywords: Mutual prodrug, combination antihypertensive therapy, loop diuretic, captopril, furosemide, ACE inhibitor, hypertension.

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