Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects

Table 2 Plasma pharmacokinetic variables of lucerastat

Study	Dose regimen		C_max [μg/mL]	t_max [h]	AUC_0–12 [μg · h/mL]	AUC_0–∞ [μg · h/mL]	t_1/2 [h]
SAD	100 mg		1.07 [0.83, 1.39]	1.25 [1.00, 3.00]	4.85 [4.13, 5.69]	5.67 [4.77, 6.71]	4.43 [3.59, 5.46]
	300 mg		2.95 [2.17, 4.01]	2.00 [1.50, 4.00]	19.12 [16.27, 22.46]	19.75 [16.81, 23.20]	4.98 [4.65, 5.33]
	500 mg		4.27 [3.75, 4.85]	2.75 [1.50, 3.50]	26.11 [22.94, 29.72]	27.27 [24.13, 30.83]	5.70 [5.11, 6.36]
	1000 mg		10.31 [6.62, 16.05]	2.25 [1.00, 3.50]	57.81 [45.07, 74.14]	60.09 [47.26, 76.41]	5.40 [4.70, 6.22]
	2x1000 mg		10.52 [7.50, 14.74]	2.00 [1.50, 2.50]	116.374 [94.74, 142.96]¹	118.01 [95.96, 145.12]	6.47 [5.42, 7.72]
MAD	200 mg	Day 1	1.99 [1.61, 2.47]	2.00 [1.00, 3.00]	9.18 [7.35, 11.48]	22.77 [19.26, 26.92]	6.10 [4.78, 7.78]
		Day 7	2.33 [1.68, 3.24]	2.00 [1.50, 3.50]	11.59 [9.72, 13.83]	28.07 [24.69, 31.91]	5.88 [4.68, 7.39]
	500 mg	Day 1	4.82 [4.41, 5.26]	2.50 [1.50, 3.50]	23.20 [20.84, 25.83]	56.87 [50.94, 63.50]	5.84 [4.88, 6.99]
		Day 7	5.18 [4.54, 5.90]	2.50 [0.50, 3.50]	29.37 [25.36, 34.00]	65.83 [56.70, 76.42]	6.33 [5.55, 7.21]
	1000 mg	Day 1	11.39 [9.06, 14.34]	2. 50 [1.50, 3.00]	51.67 [47.47, 56.24]	121.62 [112.03, 132.03]	5.41 [4.05, 7.23]
		Day 7	11.10 [8.69, 14.19]	2.50 [1.50, 4.00]	59.84 [50.97, 70.24]	132.02 [113.28, 153.87]	6.83 [5.76, 8.10]

Data are geometric means (95% CI), except for t_max, for which medians (range) are given. C _max maximum plasma concentration, t _max time to reach maximum plasma concentration, AUC _0–12 area under plasma concentration–time curve over a dosing interval (12 h), ¹area under plasma concentration–time curve from zero to 24 h; AUC _0–∞ area under plasma concentration–time curve from zero to infinity, t _1/2 terminal half–life, CI confidence interval, SAD single ascending dose, MAD multiple ascending dose

ISSN: 1750-1172