TELMISARTANCopy

• DRUGBANK - Telmisartan
• indication:

  Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Also used in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus, as well as the treatment of congestive heart failure (only in patients who cannot tolerate ACE inhibitors).

• pharmacology:

• mechanism:

  Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT<sub>1</sub>-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators.

• toxicity:

  Intravenous LD<sub>50</sub> in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.

• absorprion:

  Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food).

• halflife:

  Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.

• roouteelimination:

  Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).

• volumedistribution:

  * 500 L

• clearance:

  * >800 mL/min