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 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 13C15N-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.
Orion Corporation, Orion-Farmos Research, Espoo, Finland.
E P
EP
Sandell
M
M
Hayha
S
S
Antila
P
P
Heikkinen
P
P
Ottoila
L A
LA
Lehtonen
P J
PJ
Pentikainen
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000378:metabolism; D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006835:Hydrazones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011724:Pyridazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012016:Reference Values; D012463:Saliva / Q000378:metabolism; D000077464:Simendan; D019209:Troponin C / Q000187:drug effects / Q000502:physiology
D001798:Blood Proteins; D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019209:Troponin C; D000077464:Simendan