Pharmacokinetics of Orally and Intravenously Administered Telmisartan in Healthy Young and Elderly Volunteers and in Hypertensive Patients
| Autor: | W. Roth, Chung‐An P. F. Su, J. Stangier |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Metabolic Clearance Rate 030106 microbiology Administration Oral Angiotensin-Converting Enzyme Inhibitors Blood Pressure 030204 cardiovascular system & hematology Pharmacology Benzoates Biochemistry Gastroenterology Drug Administration Schedule 03 medical and health sciences 0302 clinical medicine Double-Blind Method Pharmacokinetics Heart Rate Reference Values Oral administration Internal medicine medicine Humans Telmisartan Dosing Young adult Infusions Intravenous Aged Cross-Over Studies business.industry Biochemistry (medical) Cell Biology General Medicine Angiotensin II Tolerability Area Under Curve Hypertension Toxicity Benzimidazoles Female business medicine.drug |
| Zdroj: | Journal of International Medical Research. 28:149-167 |
| ISSN: | 1473-2300 0300-0605 |
| DOI: | 10.1177/147323000002800401 |
| Popis: | A series of studies was conducted in healthy young males and healthy elderly males or females to evaluate the pharmacokinetic profile of telmisartan. In addition, two phase-II clinical trials assessed the pharmacokinetics and the safety of telmisartan in mild-to-moderate hypertensive patients. Telmisartan was given as a single oral (1–160 mg) or intravenous (10–160 mg) dose to young males. In another multiple-dose study, telmisartan 320 mg was administered orally once daily for 7 days to healthy young male subjects. Elderly subjects received oral telmisartan (20 and 120 mg) once daily for 7 days. Telmisartan doses of 10, 20, 40, 80, 120 and 160 mg were taken once daily by mild-to-moderate hypertensive patients for 7 days. Additionally, oral telmisartan (40, 80 or 120 mg) was administered once daily for 28 days to hypertensive subjects. Following oral dosing, median time to maximum plasma telmisartan concentration was 0.5–2 h, with maximum plasma concentrations increasing disproportionately with dose. By contrast, plasma concentrations were directly related to the intravenous dose. Steady state was observed after 5–7 days of once-daily administration, and there was no clinically relevant accumulation at 28 days. The plasma concentration-time profiles were similar in all study groups and were characterized by fast absorption and a rapid biexponential decline after the peak plasma concentration, with a prolonged terminal elimination phase (> 20 h in healthy and hypertensive subjects). Telmisartan was well tolerated, with a low incidence of drug-related adverse events. The most frequent event was headache, which also occurred in placebo-treated control subjects. No changes in heart rate, electrocardiograms or clinical chemistry were detected following receipt of telmisartan. The study thus shows that high systemic levels of telmisartan, which are well tolerated, can be attained in healthy adults of any age and in hypertensive subjects. The long terminal elimination half-life makes telmisartan suitable for once-daily dosing and contributes to the sustained efficacy over the full 24-h dosing interval. |
| Databáze: | OpenAIRE |
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