Source: Health Products Regulatory Authority (ZA) Publisher: RANBAXY (SA) (PTY) LTD, a Sun Pharma company, Ground Floor, Tugela House, Riverside Office Park, 1303 Heuwel Avenue, Centurion
A 7.1.3 Vascular medicines – other hypotensives.
Pharmacotherapeutic group: Angiotensin II Antagonists, plain
ATC Code: C09CA07
Telmisartan is a specific angiotensin II receptor (type AT1) antagonist. It displaces angiotensin II 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 at the AT1 receptor. The binding is long-lasting. Telmisartan does not inhibit human plasma renin or block ion channels.
In man, an 80 mg dose of telmisartan almost completely inhibits the angiotensin II evoked blood pressure increase. The inhibitory effect is 50% at 24 hours and still measurable up to 48 hours. After administration of the first dose of telmisartan, onset of antihypertensive activity occurs within 3 hours. The maximum reduction in blood pressure is generally attained 4-weeks after the start of treatment and is sustained during long-term therapy.
The antihypertensive effect persists over 24 hours after dosing.
There is an apparent trend to a dose relationship with regard to a time to recovery of baseline systolic blood pressure. In this respect data concerning diastolic blood pressure are inconsistent. In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate.
Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pre- treatment values over a period of several days without evidence of rebound hypertension. In reported clinical trials, telmisartan treatment has been shown to be associated with statistically significant reductions in proteinuria (including microalbuminuria and macroalbuminuria) in patients with hypertension and diabetic nephropathy.
Telmisartan treatment has been shown in clinical trials to be associated with statistically significant reductions in Left Ventricular Mass and Left Ventricular Mass Index in patients with hypertension and Left Ventricular Hypertrophy.
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 (AUC0-∞) varies from approximately 6% (40 mg dose) to approximately 19% (160 mg dose). After 3 hours post administration, plasma concentrations are similar whether telmisartan is taken fasting or with food.
The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. Gender differences in plasma concentrations were observed, Cmax and AUC being approximately 3-and 2-fold higher, respectively, in females compared to males without relevant influence on efficacy.
Telmisartan is highly bound to plasma protein (>99,5%), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 L. Telmisartan is metabolised by conjugation to the glucuronide.
No pharmacological activity has been shown for the conjugate. Telmisartan, is characterised by bi-exponential decay pharmacokinetics with a terminal elimination half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, area under the plasma concentration-time curve (AUC) increase disproportionately with dose. Plasma concentrations were higher in females than in males, without relevant influence on efficacy.
After oral administration telmisartan is nearly exclusively excreted with the faeces, mainly as unchanged compound. Cumulative urinary excretion is <2% of the dose.
Total plasma clearance (CLtot) is high (approximately 900 mL/min) when compared with hepatic blood flow (about 1 500 mL/mm).
The pharmacokinetics of telmisartan do not differ between younger and elderly patients.
Lower plasma concentrations were observed in patients with renal insufficiency undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient subjects and cannot be removed by dialysis. The elimination half-life is not changed in patients with renal impairment.
Pharmacokinetic studies 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.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.