Population pharmacokinetics of levosimendan in patients with congestive heart failure.

摘要: Aims  The aim of this study was to characterize the population pharmacokinetics levosimendan in patients with heart failure (NYHA grades III and IV) its relationship demographic factors, disease severity concomitant use digoxin β-blocking agents. Methods  Data from two efficacy studies administered by intravenous infusion were combined (190 total). data analysed using a nonlinear mixed-effects modelling approach as implemented NONMEM program. model development done three sequential steps. First best structural determined (e.g. one-, two- or three-compartment pharmacokinetic model). This followed identification incorporation important covariates into model. Lastly stochastic part refined. Results  A two-compartment described pharmacokinetics. Clearance central volume distribution found increase linearly bodyweight. No other covariates, including agents, influenced In final model, 76-kg patient estimated have clearance ± s.e. 13.3 ± 0.4 l h−1 16.8 ± 0.79 l. interindividual variability be 39% 60% for clearance distribution, respectively. Weight changed 1.5% [95% confidence interval (CI) 0.9%, 2.1%] 0.9% (95% CI 0.5%, 1.3%) per kg. Conclusions  parameters group comparable those obtained traditional methods healthy volunteers mild failure. Bodyweight which practice is accounted weight adjusting doses. None significantly levosimendan.