PHARMACOKINETICS OF LEVOSIMENDAN IN HEALTHY-VOLUNTEERS AND PATIENTS WITH CONGESTIVE-HEART-FAILURE

Levosimendan is a new inodilatory agent that sensitizes troponin-C in heart muscle cells to calcium, thus improving contractility. The pharm acokinetics of levosimendan were evaluated using a double-isotope tech nique in eight healthy volunteers and in eight patients with mild cong estive heart failure (CHF). A single i.v. dose of 0.50 mg C-14-labeled levosimendan and a single oral dose of 0.50 mg (CN)-C-13-N-15-labeled levosimendan were administered concomitantly. The elimination half-li ves (mean +/- SD) of levosimendan were 0.96 +/- 0.16 h in healthy volu nteers and 1.03 +/- 0.11 h in patients. The respective figures for tot al drug were 5.73 +/- 1.53 h and 5.23 +/- 0.99 h. Clearances of levosi mendan 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 levosi mendan 21.9 +/- 5.9 L in healthy volunteers and 19.5 +/- 4.5 L in pati ents and for C-14-drug 27.9 +/- 5.3 L and 23.8 +/- 2.8 L, respectively . The bioavailability of oral levosimendan was 85 +/- 6% in healthy vo lunteers and 84 +/- 4% in patients.