Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients.

Abstract

There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients with peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF. This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association (NYHA) Class II-IV HF. The concentrations of valsartan, sacubitril, and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate (msHR), N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF). Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50mg twice daily (BID), 100mg once daily (QD) and 100mg BID. The plasma maximum drug concentrations in the 100mg BID group were 1995 ± 1499ng/mL for valsartan, 171 ± 148ng/mL for sacubitril and 13686 ± 7418ng/mL for LBQ657. The 24h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25±10.32mmHg and 10.10±8.00mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00-18198.00) from baseline, while LVEF increased by 5.00 (-0.25-9.25) from baseline after SV treatment. PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100mg BID SV is safe and effective in patients with PD with complications of hypertension or HF.