| Indication | For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. |
| Pharmacodynamics | Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. 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. |
| Mechanism of action | The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. 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. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties. |
| Absorption | Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent. |
| Volume of distribution | Not Available |
| Protein binding | 50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound |
| Metabolism | Not substantially metabolized. 70-95% is excreted unchanged in urine via glomerular filtration and active tubular secretion. Undergoes enterohepatic recycling. |
| Route of elimination | Most of the drug is excreted in the unconverted form in the urine. |
| Half life | Approximately 14 hours. |
| Clearance | Not Available |
| Toxicity | Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma. |