Zestoretic

[Lisinopril/HCTZ]

Clinical Pharmacology
CLINICAL PHARMACOLOGY

Lisinopril and Hydrochlorothiazide

As a result of its diuretic effects, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, and decreases serum potassium. Administration of lisinopril blocks the renin-angiotensin aldosterone axis and tends to reverse the potassium loss associated with the diuretic.

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In clinical studies, the extent of blood pressure reduction seen with the combination of lisinopril and hydrochlorothiazide was approximately additive. The ZESTORETIC 10-12.5 combination worked equally well in black and white patients. The ZESTORETIC 20-12.5 and ZESTORETIC 20-25 combinations appeared somewhat less effective in black patients, but relatively few black patients were studied. In most patients, the antihypertensive effect of ZESTORETIC was sustained for at least 24 hours.

In a randomized, controlled comparison, the mean antihypertensive effects of ZESTORETIC 20-12.5 and ZESTORETIC 20-25 were similar, suggesting that many patients who respond adequately to the latter combination may be controlled with ZESTORETIC 20-12.5. (See DOSAGE AND ADMINISTRATION.)

Concomitant administration of lisinopril and hydrochlorothiazide has little or no effect on the bioavailability of either drug. The combination tablet is bioequivalent to concomitant administration of the separate entities.

ZESTORETIC ® (Lisinopril and Hydrochlorothiazide)

Lisinopril

Mechanism of Action

Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

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