ARB Duo Mechanism of Action

Pharmacology: Pharmacodynamics: Telmisartan and Amlodipine are two hypertensive compounds with complimentary mechanism to control pressure in patients with essential hypertension. An angiotensin II receptor antagonist telmisartan and a dihydropyridine calcium channel blocker, amlodipine.
The combination of these substance has an additive antihypertensive effect reducing blood pressure to a greater degree than either component alone.
Pharmacokinetics: Absorption: Absorption of Telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for Telmisartan is about 50%. When Telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve (AUC) of Telmisartan varies from approximately 6% (40mg dose) to approximately 19% (160mg dose). By 3 hours after administration, plasma concentration are similar whether Telmisartan is taken fasting or with food.
After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. Amlodipine's bioavailability is not affected by food.
Distribution: Telmisartan is largely bound to plasma protein (>99.5%), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparently volume of distribution (Vdss) is approximately 500l.
The volume of distribution of amlodipine is approximately 21 l/kg.
Biotransformation: Telmisartan is metabolized by conjugation to the glucuronide of the patient compound. No pharmacological activity has been shown for the conjugate.
Amlodipine is extensively (approximately 90%) metabolized by the liver to inactive metabolites.
Elimination: Telmisartan is characterized by biexponential decay pharmacokinetics with a terminal elimination half life of >20 hours. The maximum plasma concentration (Cmax) and to a smaller extent, the area under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no evidence of clinically relevant accumulation of Telmisartan taken at the recommended dose. Telmisartan is nearly exclusively excreted with the faeces, mainly as unchanged compound. Cumulative urinary excretions <1% of dose. Total plasma clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 1,500 ml/min).