Serum concentrations of valsartan and sacubitrilat, the active metabolite of sacubitril, in patients with heart failure with reduced ejection fraction: results of a pilot cross-sectional study.

Background: Sacubitril/valsartan is used to treat heart failure. It consists of sacubitril (its active metabolite, sacubitrilat, acts as a neprilysin inhibitor) and valsartan (an angiotensin II type 1 receptor blocker).

Research design and methods: In this study, the minimum serum concentrations of valsartan and sacubitrilat were analyzed in patients with heart failure with reduced ejection fraction.

Results: Serum concentrations of valsartan ranged from 75 to 11,700 µg/L and of sacubitrilat from 607 to 17,646 µg/L. Wide interindividual variability was observed in the serum concentrations of valsartan and sacubitrilat after administration of the same dose. Patients with NYHA class III used a significantly lower dose per day and per kilogram of body weight than those with NYHA class I/II; however, the measured concentrations of valsartan and sacubitrilat did not differ between the two groups. For both drugs, an inverse correlation was found between the weight-adjusted apparent clearance and serum creatinine and urea concentrations, sacubitrilat levels, and estimated glomerular filtration rate.

Conclusions: Valsartan and sacubitrilat concentrations showed wide inter-individual variability at the same dose, which could lead to both toxicity and suboptimal concentrations, with the risk of worsening clinical condition. Patients with reduced cardiac and renal functions are at a higher risk of overdose. [Figure: see text].