Valianz HCT Mechanism of Action

Pharmacology: Mechanism of Action: Valsartan is an angiotensin II receptor antagonist with antihypertensive activity due mainly to selective blockade of AT1 receptors and the consequent reduced pressure effect of angiotensin II. It is used in the management of hypertension.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increased plasma renin activity, increased aldosterone secretion, increased urinary potassium loss, and decreased serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
Pharmacokinetics: Valsartan is rapidly absorbed after oral doses, with a bioavailability of about 23%. Peak plasma concentrations of valsartan occur 2 to 4 hours after an oral dose. It is between 94 and 97% bound to plasma proteins. Valsartan is not significantly metabolized and is excreted mainly via the bile as unchanged drug. The terminal elimination half- life is about 5 to 9 hours following an oral dose about 83% is excreted in the faeces and 13% in urine. Hydrochlorothiazide is well absorbed (65% to 75%) following oral administration. Peak plasma concentrations are observed within 1 to 5 hours of dosing, and range from 70 to 490 mg/mL following oral doses of 12.4 to 100 mg. The plasma elimination half-life has been reported to be 6 to 15 hours, 55% to 77% of the administered dose appears in urine and greater than 95% of the absorbed dose is excreted in urine as unchanged drug.