Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized, controlled, cross-over study

Table 1 Limits for carbohydrate impurities in Lactulose formulations according to monographs in the European Pharmacopoeia

	Lactulose crystals	Lactulose liquid1
Epilactose	≤ 0.5%	≤ 10.0%
Galactose	≤ 0.5%	≤ 15.0%
Lactose	≤ 3.0%	≤ 10.0%
Fructose	≤ 0.5%	≤ 1.0%
Tagatose	≤ 0.5%	≤ 4.0%
3-Deoxy-D-glyceropentulose	-	≤ 4.0%
Total impurities	≤ 3.0%	≤ 12.0% (excluding galactose and lactose)

¹Values relative to lactulose.

Table 2 Demographic and baseline data

Variable	mean	SD
Age (yr)	35.4	13.11
BMI (kg/m²)	22.71	2.202
Venous fasting glucose level (mg/dL)	85.0	5.63
HbA1c (%)	4.98	0.297

Table 3 Summary of results of pharmacokinetic variables from analyses-of-variance: Lactulose 10 g (crystals) vs Water

Crystals	Lactulose 10 g			Water 250 mL			Treatment difference
Variable	n	LS mean	95%CI	n	LS mean	95%CI	Difference	95%CI
iAUC (mmol/L*min)	12	6.91	(-7.41; 21.24)	12	7.74	(-6.57; 22.05)	-0.822	(-19.50; 17.85)
AUC (mmol/L*min)	12	873.11	(841.26; 904.97)	12	896.86	(865.03; 928.70)	-23.75	(-51.80; 4.30)
AUC_base (mmol/L*min)	12	-50.14	(-81.99; -18.28)	12	-26.39	(-58.22; 5.45)	-23.75	(-51.80; 4.30)
C_max (mmol/L)	12	5.32	(5.12; 5.53)	12	5.36	(5.16; 5.57)	-0.04	(-0.30; 0.22)
Max_increase (mmol/L)	12	0.20	(-0.01; 0.40)	12	0.24	(0.03; 0.44)	-0.04	(-0.30; 0.22)

Table 4 Summary of results of pharmacokinetic variables from analyses-of-variance; Lactulose 20 g (crystals) vs Water

Crystals	Lactulose 20 g			Water 250 mL			Treatment difference
Variable	n	LS mean	95%CI	n	LS mean	95%CI	Difference	95%CI
iAUC (mmol/L*min)	12	12.51	(-1.74; 26.76)	12	7.74	(-6.57; 22.05)	4.772	(-13.58; 23.12)
AUC (mmol/L*min)	12	902.78	(871.02; 934.53)	12	896.86	(865.03; 928.70)	5.912	(-21.48; 33.30)
AUC_base (mmol/L*min)	12	-20.47	(-52.23; 11.28)	12	-26.39	(-58.22; 5.45)	5.912	(-21.48; 33.30)
C_max (mmol/L)	12	5.41	(5.21; 5.62)	12	5.36	(5.16; 5.57)	0.049	(-0.20; 0.30)
Max_increase (mmol/L)	12	0.28	(0.08; 0.49)	12	0.24	(0.03; 0.44)	0.049	(-0.20; 0.30)

Table 5 Summary of results of pharmacokinetic variables from analyses-of-variance: Lactulose 10 g (liquid) vs Water

Liquid	Lactulose 10 g			Water 250 mL			Treatment difference
Variable	n	LS mean	95%CI	n	LS mean	95%CI	Difference	95%CI
iAUC (mmol/L*min)	12	5.89	(-8.94; 20.72)	12	9.92	(-4.92; 24.77)	-4.029	(-20.97; 12.91)
AUC (mmol/L*min)	12	886.19	(852.75; 919.64)	12	890.45	(856.97; 923.93)	-4.258	(-33.36; 24.85)
AUC_base (mmol/L*min)	12	-53.93	(-87.38; -20.48)	12	-49.67	(-83.15; -16.19)	-4.258	(-33.36; 24.85)
C_max (mmol/L)	12	5.41	(5.17; 5.66)	12	5.49	(5.24; 5.73)	-0.073	(-0.35; 0.20)
Max_increase (mmol/L)	12	0.19	(-0.05; 0.43)	12	0.26	(0.02; 0.51)	-0.073	(-0.35; 0.20)

Table 6 Summary of results of pharmacokinetic variables from analyses-of-variance: Lactulose 20 g (liquid) vs Water

Liquid	Lactulose 20 g			Water 250 mL			Treatment difference
Variable	n	LS mean	95%CI	n	LS mean	95%CI	Difference	95%CI
iAUC (mmol/L*min)	12	11.62	(-3.21; 26.46)	12	9.92	(-4.92; 24.77)	1.701	(-15.29; 18.69)
AUC (mmol/L*min)	12	886.03	(852.58; 919.49)	12	890.45	(856.97; 923.93)	-4.419	(-33.65; 24.82)
AUC_base (mmol/L*min)	12	-54.09	(-87.55; -20.64)	12	-49.67	(-83.15; -16.19)	-4.419	(-33.65; 24.82)
C_max (mmol/L)	12	5.57	(5.33; 5.81)	12	5.49	(5.24; 5.73)	0.083	(-0.19; 0.36)
Max_increase (mmol/L)	12	0.35	(0.10; 0.59)	12	0.26	(0.02; 0.51)	0.083	(-0.19; 0.36)