Pharmacokinetics of Levosimendan in Healthy Volunteers and Patients with Congestive Heart Failure

Abstract

Levosimendan is a new inodilatory agent that sensitizes troponin-C in heart muscle cells to calcium, thus improving contractility. The pharmacokinetics of levosimendan were evaluated using a double-isotope technique in eight healthy volunteers and in eight patients with mild congestive heart failure (CHF). A single i.v. dose of 0.50 mg 14C-labeled levosimendan and a single oral dose of 0.50 mg 13C'15N-labeled levosimendan were administered concomitantly. The elimination half-lives (mean ± SD) of levosimendan were 0.96 ± 0.16 h in healthy volunteers and 1.03 ± 0.11 h in patients. The respective figures for total drug were 5.73 ± 1.53 h and 5.23 ± 0.99 h. Clearances of levosimendan averaged 359 ± 69 ml/min in healthy volunteers and 296 ± 61 ml/min in patients and of total drug 104 ± 15 and 85 ± 20 ml/min, respectively. Volumes of distribution at steady state were for levosimendan 21.9 ± 5.9 L in healthy volunteers and 19.5 ± 4.5 L in patients and for 14C-drug 27.9 ± 5.3 L and 23.8 ± 2.8 L, respectively. The bioavailability of oral levosimendan was 85 ± 6% in healthy volunteers and 84 ± 4% in patients.