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Pharmacology: Valsartan is a nonpeptide, orally active and specific angiotensin II antagonist acting on the AT1 receptor subtype. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the 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 increases in plasma rennin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The rennin-aldosterone link is mediated by angiotensin II, so co-administration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.
Pharmacokinetics: Valsartan is rapidly absorbed following oral administration, 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 of about 83% is excreted in the feces and about 13% in urine.
Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. It is reported to have a bioavailability of about 65 to 70%. It has been estimated to have a plasma half-life of between about 5 and 15 hours and appears to be preferentially bound to red blood cells. It is excreted mainly unchanged in the urine. Hydrochlorothiazide crosses the placental barrier and is distributed into breast milk.
