Clin Pharmacokinet. 2026 Apr 29. doi: 10.1007/s40262-026-01647-z. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVE: Cardiovascular risk is markedly increased in end-stage renal disease. Although sacubitril/valsartan provides cardiovascular benefits in heart failure, evidence supporting its use in end-stage renal disease, particularly in patients undergoing peritoneal dialysis, remains limited. This study aimed to characterize the pharmacokinetics of sacubitril/valsartan in patients with heart failure and end-stage renal disease undergoing peritoneal dialysis and to determine whether dose adjustment is warranted.
METHODS: In this prospective study, plasma, urine, and peritoneal dialysate samples were collected from 40 patients with heart failure and end-stage renal disease undergoing peritoneal dialysis, and population pharmacokinetic models were developed to simultaneously characterize valsartan and LBQ657 pharmacokinetic profiles across the three matrices. Covariates' effects were quantitatively evaluated using a forest plot. Renal and peritoneal dialysate excretion fractions of valsartan and LBQ657 were estimated based on population pharmacokinetic models.
RESULTS: A one-compartment model with first-order absorption and elimination, incorporating urinary excretion and bidirectional exchange with peritoneal dialysate, was developed to characterize the pharmacokinetics of valsartan and LBQ657 in patients with end-stage renal disease. Fat-free mass was a key determinant of non-renal clearance and exposure for both analytes. A covariate analysis showed that, relative to the median fat-free mass (42.2 kg), a fat-free mass of 58.95 kg was associated with a 54% lower valsartan area under the concentration-time curve during steady state and a 26% lower LBQ657 area under the concentration-time curve during steady state. Urinary and peritoneal dialysate eliminations of valsartan and LBQ657 were minimal, not exceeding 1% and 7%, respectively.
CONCLUSIONS: The population pharmacokinetic models for valsartan and LBQ657 adequately characterized profiles in plasma, urine, and peritoneal dialysate in patients with heart failure and end-stage renal disease undergoing peritoneal dialysis. In this special population, the impact of peritoneal dialysis was minimal, and no dose adjustment is required based on peritoneal dialysis status.
CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier no. ChiCTR2200055924.
PMID:42053769 | DOI:10.1007/s40262-026-01647-z