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Mykrox

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Mykrox

CLINICAL PHARMACOLOGY

MYKROX (metolazone) is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of MYKROX (metolazone) result from interference with the renal tubular mechanism of electrolyte reabsorption. MYKROX (metolazone) acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. MYKROX (metolazone) does not inhibit carbonic anhydrase. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.

In two double-blind, controlled clinical trials of MYKROX (metolazone) Tablets, the maximum effect on mean blood pressure was achieved within 2 weeks of treatment and showed some evidence of an increased response at 1 mg compared to ½ mg. There was no indication of an increased response with 2 mg.

After six weeks of treatment, the mean fall in serum potassium was 0.42 mEq/L at ½ mg, 0.66 mEq/L at 1 mg, and 0.7 mEq/L at 2 mg. Serum uric acid increased by 1.1 to 1.4 mg/dL at increasing doses. There were small falls in serum sodium and chloride and a 1.3-2.1 mg/dL increase in BUN at increasing doses.

The rate and extent of absorption of metolazone from MYKROX (metolazone) Tablets were equivalent to those from an oral solution of metolazone. Peak blood levels are obtained within 2 to 4 hours of oral administration with an elimination half-life of approximately 14 hours. MYKROX (metolazone) Tablets have been shown to produce blood levels that are dose proportional between ½ -2 mg. Steady state blood levels are usually reached in 4-5 days.

In contrast, other formulations of metolazone produce peak blood concentrations approximately 8 hours following oral administration; absorption continues for an additional 12 hours.

Last reviewed on RxList: 5/4/2009
This monograph has been modified to include the generic and brand name in many instances.

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