| 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). |
| Pharmacodynamics |
Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It has the highest affinity for the AT1 receptor among commercially available ARBS and has minimal affinity for the AT2
receptor. New studies suggest that telmisartan may also have PPARγ
agonistic properties that could potentially confer beneficial metabolic
effects, as PPARγ is a nuclear receptor that regulates specific gene
transcription, and whose target genes are involved in the regulation of
glucose and lipid metabolism, as well as anti-inflammatory responses.
This observation is currently being explored in clinical trials.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by
angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the
principal pressor agent of the renin-angiotensin system, with effects
that include vasoconstriction, stimulation of synthesis and release of
aldosterone, cardiac stimulation, and renal reabsorption of sodium.
Telmisartan works by blocking the vasoconstrictor and aldosterone
secretory effects of angiotensin II. |
| Mechanism of action |
Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-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. |
| Absorption |
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). |
| Volume of distribution |
|
| Protein binding |
Highly bound to plasma proteins (>99.5%), mainly albumin and a1-acid glycoprotein. Binding is not dose-dependent. |
| Metabolism |
Minimally metabolized by conjugation to form a pharmacologically
inactive acylglucuronide; the glucuronide of the parent compound is the
only metabolite that has been identified in human plasma and urine. The
cytochrome P450 isoenzymes are not involved in the metabolism of
telmisartan. |
| Route of elimination |
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). |
| Half life |
Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. |
| Clearance |
|
| Toxicity |
Intravenous LD50 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. |
