A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults

Figures & data

Figure 1. Study flow diagram.

Table 1. Demographics and baseline characteristics.

	Sequence E → I (n = 9) mean (SD) or %	Sequence I → E (n = 9) mean (SD) or %
Age, years	42 (17)	38 (14)
% Male/Female	44/56	56/44
% White/Asian/Other	56/33/11	78/11/11
Body weight, kg	71.4 (11.3)	77.9 (17.5)
Body mass index, kg/m^2	25.5 (2.0)	26.2 (1.9)
Systolic blood pressure, mmHg	115 (13)	123 (8)
Diastolic blood pressure, mmHg	74 (10)	77 (6)
Heart rate, bpm	63 (10)	66 (10)

Figure 2. Total plasma melatonin concentrations. Data are mean ± SD at pre-dose (0 h) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, and 10 h post-dose for participants in the PP population (n = 17). PP: per protocol; SD: standard deviation.

Table 2. Comparison of pharmacokinetic parameters of extended-release and immediate-release melatonin.

Parameter	Extended-release mean (SD)	Immediate-release mean (SD)	P-value
AUC0-10h (pg.h/mL)	17181 (19217)	16711 (11353)	0.417
Tmax (h)	1.56 (0.55)	0.60 (0.40)	<0.001
Cmax (pg/mL)	7581 (9743)	13120 (9959)	0.002
ka (h^-1)	12040 (12735)	50605 (43082)	<0.001
λ (h^-1)	0.44 (0.08)	0.77 (0.18)	<0.001
ta1/2 (h)	1.57E-04 (1.76E-04)	3.10E-05 (3.54E-05)	0.002
t1/2 (h)	1.63 (0.28)	0.95 (0.28)	<0.001

Abbreviations: AUC_0-10h, area under the curve; t_max, time to peak concentration; c_max, peak concentration; k_a, absorption rate constant; λ, elimination rate constant; t_a1/2, absorption half-life; t_1/2, elimination half-life.