. 2024 Jan 17;72(4):2154–2164. doi: 10.1021/acs.jafc.3c06431

Table 2. Pharmacokinetic Parameters of the Metabolites of Hydroxytyrosol Estimated by Noncompartmental Analysis¹,².

		hydroxytyrosol sulfate M1-a		hydroxytyrosol sulfate M1-b
parameters	units	30 olives group	60 olives group	30 olives group	60 olives group
C_max	(nmol/L)	47.34 (27.47, 81.60)^a	97.35 (64.97, 145.9)^b	306.4 (182.2, 515.3)^a	548.4 (382.3, 786.5)^b
C_max/D		0.00899 (0.00522, 0.01546)^a	0.00872 (0.00562, 0.01354)^a	0.0582 (0.0343, 0.0985)^a	0.0491 (0.0333, 0.0726)^a
T_max	min	45.5 (30, 120)^a	36 (30, 42)^a	30.50 (30,120)^a	38 (30, 100)^a
AUC_t	min·nmol/L	4321 (3152, 5924)^a	11376 (8674, 14919)^b	26907 (19824, 36520)^a	67548 (53591, 85140)^b
AUC_t/D		0.82 (0.60, 1.11)^a	1.02 (0.75, 1.38)^a	5.11 (3.78, 6.90)^a	6.05 (4.76, 7.70)^a
AUC_0–∞	min·nmol/L	4765 (3491, 6504)^a	13133 (9812, 17577)^b	28084 (20399, 38664)^a	80006 (65787, 97299)^b
AUC_0–∞/D		0.90 (0.68, 1.23)^a	1.18 (0.84, 1.64)^a	5.33 (3.89, 7.31)^a	7.17 (5.62, 9.14)^a
AUC_0–∞m/AUC_0–∞		1.11 (0.81, 1.52)^a	1.47 (0.88, 2.46)^a	6.54 (4.82, 8.8)^a	8.97 (5.97, 13.47)^a
λ_z	(1/min)	0.0053 (0.0026, 0.011)^a	0.0054 (0.0034, 0.0083)^a	0.0080 (0.0063, 0.01024)^a	0.0054 (0.0031, 0.0094)^a
t_1/2λz	min	130.1 (64.5, 262.2)^a	129.4 (83.0, 201.6)^a	86.4 (67.7, 110)^a	129.3 (74.1, 225.6)^a
MRT_0–∞	min	173 (121.9, 245.5)^a	188.3 (143.6, 246,9)^a	141.4 (118.1, 169.3)^a	198.8 (139.0, 284.3)^a
Vss/F·fm	L/kg	616 (339, 1120)^a	548 (380, 789)^a	96.4 (62.6, 148)^a	83.5 (61.6, 112.9)^a
Vd_area/F·fm	L/kg	491 (190, 1264)^a	479 (290, 790)^a	85.0 (57.2, 126)^a	75.1 (45.7, 123)^a
Cl/F·fm	L/min/kg	4.02 (2.95, 5.48)^a	2.91 (2.17, 3,89)^a	0.68 (0.49, 0.94)^a	0.48 (0.39, 0.58)^a

		hydroxytyrosol glucuronide M2-a		hydroxytyrosol glucuronide M2-b
parameters	units	30 olives group	60 olives group	30 olives group	60 olives group
C_max	(nmol/L)	9.46 (5.99, 14.95)^a	14.19 (9.34, 21.46)^a	5.41 (3.30, 8.89)^a	8.97 (6.16, 13.06)^a
C_max/D		0.00180 (0.00114, 0.00283)^a	0.00127 (0.00081, 0.00201)^a	0.00103 (0.0006, 0.0017)^a	0.00080 (0.00052, 0.00124)^a
T_max	min	45.5 (30, 120)^a	41 (30, 123)^a	45.5 (30, 120)^a	38 (30, 91)^a
AUC_t	min·nmol/L	1017 (845, 1224)^a	1953 (1617, 2359)^b	615.9 (475, 799)^a	1161 (912.4, 1476)^b
AUC_t/D		0.19 (0.16, 0.23)^a	0.18 (0.14, 0.22)^a	0.12 (0.09, 0.15)^a	0.10 (0.07, 0.14)^a
AUC_0–∞	min·nmol/L	1059 (862, 1301)^a	2234 (1882, 2652)^b	641.9 (491.1, 839.0)^a	1239 (939.4, 1635)^b
AUC_0–∞/D		0.20 (0.17, 0.24)^a	0.20 (0.16, 0.25)^a	0.12 (0.09, 0.16)^a	0.11 (0.079, 0.156)^a
AUC_0–∞m/AUC_0–∞		0.25 (0.20, 0.30)^a	0.25 (0.18, 0.35)^a	0.15 (0.12, 0.19)^a	0.14 (0.08, 0.22)^a
λ_z	(1/min)	0.0080 (0.0051, 0.0124)^a	0.0062 (0.0039, 0.0010)^a	0.0082 (0.0051, 0.0131)^a	0.0078 (0.0050, 0.0122)^a
t_1/2λz	min	86.92 (55.62, 135.9)^a	111.8 (69.6, 179.6)^a	84.84 (52.83, 136.2)^a	88.58 (57.00, 137.7)^a
MRT_0–∞	min	142.8 (120.9, 168.7)^a	185.6 (132.9, 259.2)^a	138.8 (109.5, 17661)^a	149.2 (123.1, 180.7)^a
Vss/F·fm	L/kg	2580 (1950, 3414)^a	2791 (2084, 3721)^a	4139 (2668, 6420)^a	4598 (3507, 6029)^a
Vd_area/F·fm	L/kg	2266 (1435, 3579)^a	2386 (1497, 3803)^a	3649 (2081, 6396)^a	3940 (2433, 6380)^a
Cl/F·fm	L/min/kg	18.1 (14.7, 22.2)^a	17.1 (14.4, 20,3)^a	29.8 (22.8, 38.9)^a	30.8 (23.4, 40.7)^a

Plasma concentrations were obtained after a single oral administration to Sprague-Dawley rats of Arbequina table olives containing hydroxytyrosol at 2.95 mg/kg (30 olives group) and 5.89 mg/kg (60 olives group).

Results are expressed as geometric means (95% CIs) except for T_max which is presented as the median with its minimum and maximum value in the 30 olives (n = 6) and 60 olives (n = 7) groups. Data were analyzed by unpaired-Student t-test except for T_max in which a nonparametric Wilcoxon signed-rank test was used. Within the same compound, means without a common letter differ, p < 0.05. AUC_0-∞, area under the plasma concentration–time curve from time zero to infinite; AUC_t: area under the plasma concentration–time curve from time zero up to 8h; AUC_0-∞m/AUC_0-∞, ratio of the relative exposure of each metabolite with respect to hydroxytyrosol; C_max, peak plasma concentration; Cl/F·fm, apparent clearance of metabolite; D, dose of hydroxytyrosol; MRT_0-∞, mean residence time from zero to infinite; T_max, time to peak plasma concentration; t_1/2λz, apparent elimination half-life; V_ss/F·fm, apparent steady-state volume of distribution of metabolite; Vd_area/F·fm, apparent volume of distribution associated with the terminal phase of the plasma concentration–time curve of metabolite; λ_z, apparent elimination rate constant.

Table 2. Pharmacokinetic Parameters of the Metabolites of Hydroxytyrosol Estimated by Noncompartmental Analysis1,2.

Table 2. Pharmacokinetic Parameters of the Metabolites of Hydroxytyrosol Estimated by Noncompartmental Analysis¹,².