Integrated pharmacokinetics and pharmacodynamics of the novel calcium sensitizer levosimendan as assessed by systolic time intervals

International Journal of Clinical Pharmacology and Therapeutics

Volumn 36, Issue 12, 1998, Pages 629-635

  Sundberg, S ^a   Antila, S ^a   Scheinin, H ^b   Hayha M ^a   Virtanen, M ^a   Lehtonen, L ^a  

^a ORION CORPORATION   (Finland)

^b TURKU UNIVERSITY HOSPITAL   (Finland)

Author keywords

Calcium sensitizers; Levosimendan; Pharmacokinetic pharmacodynamic modelling; Systolic time intervals

Indexed keywords

CALCIUM SENSITIZER; LEVOSIMENDAN;

ADULT; ARTICLE; CLINICAL TRIAL; CROSSOVER PROCEDURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG FORMULATION; DRUG HALF LIFE; HEART OUTPUT; HEART RATE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN EXPERIMENT; HYSTERESIS; IMPEDANCE CARDIOGRAPHY; INOTROPISM; INTRAVENOUS DRUG ADMINISTRATION; MALE; PHARMACODYNAMICS; SLOW RELEASE FORMULATION; SYSTOLIC TIME INTERVAL; TABLET;

ADMINISTRATION, ORAL; ADULT; BIOLOGICAL AVAILABILITY; CARDIAC OUTPUT; CARDIOTONIC AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CROSS-OVER STUDIES; DELAYED-ACTION PREPARATIONS; HEART RATE; HUMANS; HYDRAZONES; INFUSIONS, INTRAVENOUS; MALE; MODELS, CHEMICAL; PYRIDAZINES; REFERENCE VALUES; TABLETS; VASCULAR RESISTANCE;

EID: 0031775152     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (22)

1. Belz GG, Stern HC, Butzer K 1985 Dose-response following single administration of a new cardiac performance enhancer RO 13-6438 in normal volunteers. J Cardiovasc Pharmacol 7: 86-90
2. Buch J, Waldorff S, Hansen PO, Rasmussen OO 1983 Noninvasive measuring of the circulatory effect of afterload reduction in order to monitor the pharmacodynamic effect of drugs in normal volunteers. Br Heart J 50: 170-175
3. De Mey C, Belz GG, Nixdorf U, Butzer R, Schroeter V, Meyer J, Erbel R 1992 Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproteronol in healthy volunteers. Clin Pharmacol Ther 52: 609-619
4. Galeazzi RL, Benet LZ, Sheiner LB 1976 Relationship between the pharmacokinetics and pharmacodynamics of procainamide. Clin Pharmacol Ther 20: 278-289
5. Holford NHG, Sheiner LB 1981 Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 6: 429-453
6. Inturrisi CE, Portenoy RK, Max MB, Colburn WA, Foley KM 1990 Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain. Clin Pharmacol Ther 47: 565-577
7. Karlsson M, Korkolainen T, Wikberg T 1997 Automated analysis of levosimendan in human plasma by on-line dialysis and liquid chromatography. Biomed Chromatogr 11: 54-58
8. Lilleberg J, Sundberg S, Häyhä M, Akkila J, Nieminen MS 1994a Haemodynamic dose-efficacy of levosimendan in healthy volunteers. Eur J Clin Pharmacol 47: 267-274
9. Lilleberg J, Antila S, Karlsson M, Nieminen MS, Pentikäinen PJ 1994b Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Clin Pharmacol Ther 56: 554-563
10. Lilleberg J, Sundberg S, Nieminen MS 1995 Dose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction. J Cardiovasc Pharmacol 26 (Suppl 2): S63-S69
11. Pollesello P, Ovaska M, Kaivola J, Tilgman C, Lundström K, Kalkkinen N, Ulmanen I, Nissinen E, Taskinen J 1994 Binding of a new Ca-sensitizer, levosimendan, to recombinant human cardiac troponin C. A molecular modelling, fluorescence probe and proton nuclear magnetic resonance study. J Biol Chem 269: 28584-28590
12. Ritschel WA 1986 Handbook of basic pharmacokinetics (3rd edn). Drug Intelligence Publishers Inc, Hamilton
13. Sandell E-P, Häyhä M, Antila S, Heikkinen P, Ottoila P, Lehtonen LA, Pentikäinen PJ 1995 Pharmacokinetics of levosimendan in healthy volunteers and patients with congestive heart failure. J Cardiovasc Pharmacol 26 (Suppl 2): S57-S62
14. Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J 1979 Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 25: 358-371
15. Spodick DH, Lance VQ 1976 Noninvasive stress testing - Methodology for elimination of the phonocardiogram. Circulation 53: 673-676
16. Sramek BB 1989 Haemodynamic and pump-performance monitoring by electrical bioimpedance. New concepts. Prob Respir Care 2: 274-290
17. Stern HC, Matthews JF, Belz GG 1984 Influence of dihydralazine induced afterload reduction on systolic time intervals and echocardiography in healthy subjects. Br Heart J 52: 435-439
18. Sundberg S 1993 Short- and long-term variation of systolic and diastolic time intervals at rest and during dynamic exercise in healthy subjects. Am J Noninvas Cardiol 7: 301-305
19. Sundberg S, Lilleberg J, Nieminen MS, Lehtonen L 1995 Hemodynamic and neurohumoral effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men. Am J Cardiol 75: 1061-1066
20. Van Peer A, Snoeck E, Huang M-L, Heykants J 1993 Pharmacokinetic-pharmacodynamic relationships in phase I/phase II of drug development. Eur J Drug Metab Pharmacokinet 18: 49-59
21. Weissler AM, Harris WS, Schoenfeld CD 1968 Systolic time intervals in heart failure in man. Circulation 37: 149-159
22. + channel in rat arterial myocytes. Eur J Pharmacol 333: 249-259