Effect Of Different Degrees Of Hepatic Dysfunction On The Pharmacokinetics Of Telmisartan

Abstract

Background: Hypertension is a highly prevalent condition, as well as being one of the most powerful contributors to cardiovascular diseases; hypertension is also the leading cause of death in developed countries. Angitensin II receptor blockers represent a new class of effective and well tolerated orally active antihypertensive agents. Telmisartan is a nonpeptide angitensin II receptor antagonist, used for the treatment of hypertension. Objective: To describe the pharmacokinetics and safety of telmisartan in healthy volunteers and in subjects with different degree of hepatic impairment. Setting: Tanta University Hospitals, Faculty of Pharmacy, Ain Shams University and Faculty of Pharmacy, Tanta University, Egypt. Design: Prospective study. Single oral dose of telmisartan 80 mg was given to 10 healthy subjects served as a control group (group 1), and 20 subjects with hepatic impairment; divided into two groups; group 2(10 patients): patients with mild hepatospleenomegaly and group 3 (10 patients): patients with cirrhosis and ascitis. Plasma samples were collected and analyzed with high performance liquid chromatography (HPLC). Main outcome measures: Cmax, tmax, t 1/2, MRT, AUC0-∞, Cl/F and Vdss Results: The pharmacokinetic profile of telmisartan was characterized by rapid absorption kinetics and a slow terminal elimination phase with mean half life of 25 hours. The maximum plasma concentration and area under the telmisartan plasma concentration-time curve (AUC0-∞} increased in all hepatically impaired subjects compared with healthy volunteers. There was a significant increase in the Cmax and AUC0-∞ of the cirrhotic patients and non significant increase in the patients with mild hepatospleenomegaly compared with the healthy volunteers. There was no change in the half life of telmisartan in all the patients and no adverse events were noticed in the patients during the study indicating the good tolerability of the drug in hypertensive patients with hepatic dysfunction. Conclusion: Lower doses of telmisartan should be considered in cirrhotic patients as well as in the patients with mild hepatitis.


Egyptian Journal of Biomedical Sciences Vol. 23 (1) 2007: pp. 257-265