Table 4.

Summary statistics for pharmacokinetic (PK) parameters in plasma and cerebrospinal fluid (CSF) for LCZ696 analytes (sacubitril, LBQ657 and valsartan) (PK analysis set)

	AUC(0,τ ,ss) (ng ml‐1 h)	C max (ng ml‐1 )	C trough * (ng ml‐1 )	t max (h)
Plasma, n	19	19	19	19
Sacubitril Mean (SD) CV% Mean Median Min–max	3220 (1530) 47.5 3010 1030–7830	1710 (682) 39.9 1740 553–3150	0.412 (0.787) 191.0 0 0–2.83	NA NA 1.00 1.00–4.00
LBQ657 Mean (SD) CV% Mean Median Min–max	137 000 (39 400) 28.7 131 000 66 800–218 000	14 100 (3600) 25.5 14 200 7790–19 600	1840 (907) 49.3 1710 455–3720	NA NA 2.00 1.00–4.00
Valsartan Mean (SD) CV% Mean Median Min–max	21 300 (11 200) 52.8 19 400 7940–49 500	3910 (2100) 53.7 3420 1030–9380	180 (113) 62.9 145 57.7–532	NA NA 1.03 1.00–2.05
CSF, n	16†	17‡	16†	17‡
LBQ657 Mean (SD) CV% Mean Median Min–max	387 (261) 67.4 338 154–1290	19.2 (11.3) 58.9 17.9 9.09–58.8	13.2 (12.4) 94.0 10.2 3.93–56.6	NA NA 8.00 3.98–12.0

^* For all analytes in both plasma and CSF, C _trough was observed at 24 h post‐dose.

^† Data from three subjects were excluded due to insufficient concentration data for estimation of AUC(0,τ) and C _trough.

^‡ All PK parameters from two subjects were excluded from summary statistics due to insufficient concentration data.

AUC, area under the curve; C _max, maximum plasma concentration; CSF, cerebrospinal fluid; C _trough, trough plasma concentration; CV, coefficient of variation; NA, not available; PK, pharmacokinetic; SD, standard deviation; t _max, time to maximum concentration