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Pharmacokinetics and Safety of Intravenous and Oral Telmisartan 20 mg and 120 mg in Subjects with Hepatic Impairment Compared with Healthy Volunteers
Author(s) -
Stangier Joachim,
Su ChungAn P. F.,
Schöndorfer G.,
Roth Willy
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000004001207
Subject(s) - telmisartan , pharmacokinetics , medicine , oral administration , bioavailability , dosing , pharmacology , adverse effect , cmax , blood pressure
The pharmacokinetics and safety of telmisartan were assessed in subjects with hepatic impairment in a single‐center, open‐label study. Single oral doses of telmisartan 20 mg and 120 mg, separated by a washout period of 14 days, were given to 12 hepatically impaired subjects and 12 healthy subjects. In 5 hepatically impaired subjects who received both oral doses, a single IV infusion of telmisartan 120 mg was later administered. After oral dosing, the pharmacokinetic profile of telmisartan was characterized by rapid absorption and disposition kinetics and a slow terminal elimination phase with mean half‐lives of 27 to 42 hours. The maximum plasma concentration and area under the telmisartan plasma concentration‐time curve (AUC 0‐∞ ) increased in hepatically impaired subjects compared with healthy volunteers 6.4‐fold and 2.7‐fold, respectively, for telmisartan 20 mg and 3.2‐fold and 3.1‐fold, respectively, for telmisartan 120 mg. Maximum plasma concentrations and AUC 0‐∞ after IV infusion were markedly elevated compared with values obtained from other studies conducted in healthy volunteers. Hepatic impairment resulted in an apparent increase in the absolute bioavailability of telmisartan, and total clearance following oral and IV administration was significantly reduced compared with healthy volunteers. Plasma protein binding of telmisartan was ≥ 99.5% in hepatically impaired and healthy subjects and was not changed when compared to healthy subjects. Oral and IV telmisartan were well tolerated in both the hepatically impaired and the healthy; headache was the most common potentially telmisartan‐related adverse event. Changes in vital signs and clinical laboratory parameters were transient and of no clinical relevance. The good tolerability of telmisartan in hepatically impaired patients demonstrated in this study, the proven sustained blood pressure control in hypertensive patients, and the increased exposure in patients with hepatic dysfunction suggest that effective treatment of hypertensive patients with impaired hepatic function would be achieved even with the lowest dose of telmisartan available. The increased bioavailability of telmisartan suggests that lower doses of telmisartan should be considered when the drug is administered to patients with hepatic impairment .