||Aliskiren fumarate; Aliskiren (hemifumarate); UNII-C8A0P8G029; CHEBI:53777
||Aliskiren hemifumarate is an orally bioactive renin inhibitor (human IC50 = 0.6 nM; rat IC50 = 80 nM) appearing to bind to both the hydrophobic S1/S3-binding pocket and to a large, distinct subpocket that extends from the S3-binding site towards the hydrophobic core of renin. It exhibits an inhibitory activity for arterial vasoconstriction and aldosterone production.
1. Simultaneous Determination of Aliskiren, Amlodipine and Hydrochlorothiazide in Spiked Human Plasma and Urine by High Performance Liquid Chromatography
Zeynep Aydomugs. Journal of Analytical Chemistry, 2015, Vol. 70, No. 4, pp. 502–509.
Aliskiren hemifumarate (Scheme) is the direct rennin enzyme inhibitor clinically used in treatment of hypertension either alone or in combination with other antihypertensive agents. After administration, ALS is rapid ly absorbed with peak plasma concentration occurring after 1–3 h. Its bioavailability is about 2.6% and it is eliminated unchanged primarily by the biliary-fecal route (91%) and renal excretion is only about 0.6%.
2. Ion‑Pair LC Method for Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Pharmaceuticals
Ramzia I. El‑Bagary • Gabor Patonay • Asmaa A. Elzahr • Ehab F. Elkady • Walid A. Ebeid. Chromatographia (2014) 77:257–264
Aliskiren hemifumarate (ALS) (2S,4S,5S,7S)-N-(2-carba-moyl-2-methylpropyl)-5-amino-4-hydroxy-2,7 diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy) phenyl]octanamide hemifumarate) (Fig. 1a), is the first direct renin inhibitor (DRI) suitable for oral administration. By achieving more complete renin–angiotensin system inhibition, direct renin inhibitors may afford greater protection from hypertensive complications. Present evidence indicates that aliskiren reduces baseline systolic and diastolic blood pressure and that it is as effective as other first-line anti-hypertensive agents. Extra advantages can be reached when it is used in combination therapy. Amlodipine besylate (AML) (3-ethyl-5-methyl-(4RS)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate benzenesulfonate) (Fig. 1b), is a dihydropyridine long-acting calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Hydrochlorothiazide is a potent orally diuretic and anti-hypertensive agent which inhibits active chloride reabsorption and thus increases the excretion of sodium chloride and water. It is chemically 6-chloro-1,1-dichloro-3,4-dihydro-2H-1,2,4-benzoliadiazine-7-sulfanomide-1,1-dioxide (Fig. 1c). Triple combination therapy of Aliskiren hemifumarate (ALS), AML and HCZ proved to be effective and well tolerated in treating hypertensive high-risk patients.