Pharmacokinetics and safety of intravenous and oral telmisartan 20 mg and 120 mg in subjects with hepatic impairment compared with healthy volunteers

The pharmacokinetics and safety of telmisartan were assessed in subjects wi th hepatic impairment in a single-center, open-label study Single oral dose s 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. I n 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 absor ption and disposition kinetics and a slow terminal elimination phase with m ean half-lives of 27 to 42 hours. The maximum plasma concentration and area under the telmisartan plasma concentration-time curve (AUC(0-infinity)) in creased 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 concentration s and AUC(0-infinity) after IV infusion were markedly elevated compared wit h values obtained from other studies conducted in healthy volunteers. Hepat ic impairment resulted in an apparent increase in the absolute bioavailabil ity of telmisartan, and total clearance following oral and IV administratio n was significantly reduced compared with healthy volunteers. Plasma protei n binding of telmisartan was greater than or equal to 99.5% in hepatically impaired and healthy subjects and was not changed when compared to healthy subjects. Oral and TV telmisartan were well tolerated in both the hepatical ly impaired and the healthy; headache was the most common potentially telmi sartan-related adverse event. Changes in vital signs and clinical laborator y parameters were transient and of no clinical relevance, The good tolerabi lity of telmisartan in hepatically impaired patients demonstrated in this s tudy, the proven sustained blood pressure control in hypertensive patients, and the increased exposure in patients with hepatic dysfunction suggest th at effective treatment of hypertensive patients with impaired hepatic funct ion would be achieved even with the lowest dose of telmisartan available. T he increased bioavailability of telmisartan suggests that lower doses of te lmisartan should be considered when the drug is administered to patients wi th hepatic impairment. (C) 2000 the American College of Clinical Pharmacology.