Telgio Mechanism of Action

Pharmacology: Pharmacodynamics: Telmisartan is an orally effective and specific angiotensin II receptor (type AT₁) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT₁ receptor subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT₁ receptor. Telmisartan selectively binds the AT₁ receptor. The binding is long lasting.
Telmisartan does not show affinity for other receptors, including AT₂ and other less characterized AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse effects.
Pharmacokinetics: Telmisartan is well absorbed following oral administration. Telmisartan tablet has been studied in a randomized, open-label, three-period, three-sequence partial replicate design study under fasting conditions which included 30 healthy adult male and female subjects.
After oral administration of 80 mg telmisartan tablet, the mean of AUC_0-72h was 5,089.1 ng.hour/mL. The mean of maximum plasma concentration (C_max) was 1,018.44 ng/mL and reached within 0.88 hours (0.50-2.00 hours). The mean elimination half-life (t_½) of telmisartan tablet was 24.36 hours. The geometric mean ratios (90% confidence intervals) of telmisartan tablet were 101.65% (96.33-107.27%) for AUC_0-72h and 84.17% (73.01-97.03%) for C_max. The result of this study showed that the pharmacokinetic parameters of telmisartan tablet were within the acceptance range for bioequivalence, therefore, telmisartan tablet were similar or bioequivalent to the reference drug.
Elderly patients: The pharmacokinetics of telmisartan do not differ in younger and elderly patients.
Patients with renal impairment: Lower plasma concentrations were observed in patients with renal insufficiency undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and cannot be removed by dialysis. The elimination half-life is not changed in patients with renal impairment.
Patients with hepatic impairment: Pharmacokinetic profile of telmisartan in patients with hepatic impairment showed an increase in absolute bioavailability up to nearly 100%. The elimination half-life is not changed in patients with hepatic impairment.
Pediatric population: The pharmacokinetics assessment are generally consistent with the findings in adults and confirm the nonlinearity of telmisartan, particularly for C_max.