Inhibitory Effect of Telmisartan on the Blood Pressure Response to Angiotensin II Challenge
| Autor: | Thomas Meinicke, Henrieke de Bruin, Jan J. van Lier, Joachim Stangier, Pauline N. M. Van Heiningen, W.J Tamminga, Chung‐An P. F. Su, Jan H. G. Jonkman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Angiotensin-Converting Enzyme Inhibitors Blood Pressure Pharmacology Placebo Benzoates Angiotensin Receptor Antagonists Double-Blind Method Pharmacokinetics Oral administration Internal medicine Renin–angiotensin system medicine Humans Telmisartan Pulse Aldosterone business.industry Angiotensin II Headache Plethysmography Endocrinology Blood pressure Area Under Curve Hypertension Benzimidazoles Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 38:672-685 |
| ISSN: | 0160-2446 |
| Popis: | Telmisartan is a new angiotensin receptor antagonist possessing potent, selective, and insurmountable inhibitory activity specific to the angiotensin II type 1 (AT 1 ) receptor. The current study was performed to determine the inhibition of the angiotensin II pressor response by telmisartan in 48 healthy volunteers challenged with hypertension-inducing doses of i.v. angiotensin II. Subjects were challenged with this dose of angiotensin II at intervals between 0.25 and 48 h after double-blind single-dose oral administration of telmisartan 20 mg (n = 12), 40 mg (n = 12), or 80 mg (n = 12) or placebo (n = 12) in parallel groups. Diastolic and systolic blood pressure and pulse rate were recorded continuously using a servophotoplethysmograph. Urine samples were collected during the study for urinalysis. Tolerability of telmisartan, in comparison with placebo, was also monitored throughout the study. Telmisartan 20-80 mg dose dependently inhibited the increase in diastolic and systolic blood pressure induced by angiotensin II. Telmisartan 40 mg produced 80.1% maximum inhibition, and with 80 mg 89.6% maximum inhibition of diastolic blood pressure was achieved. Inhibition was apparent after 0.3-1.1 h and was still observed 48 h after administration for all telmisartan doses. The inhibitory effect of telmisartan 20, 40, and 80 mg, 48 h after dosing was significantly greater than that of placebo. A > 25% inhibition of the angiotensin II response on diastolic blood pressure was detected until 26.9, 35.4, and 40.5 h, respectively, after telmisartan 20 mg, 40 mg, and 80 mg. Anti-clockwise hysteresis was observed, indicating a delay and longer persistence of effect than to be expected from the plasma concentration-time course. The slow dissociation of telmisartan from the receptor probably contributed to this hysteresis. The incidence of adverse events was comparable in telmisartan-and placebo-treated subjects and was not dose dependent. In conclusion, telmisartan 40 mg provides rapid-onset, well-tolerated, and near-maximal inhibition of angiotensin II-induced hypertension, with maintenance of the inhibitory effect for 48 h. |
| Databáze: | OpenAIRE |
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