Effects of nutritional status on acetaminophen measurement and exposure

Figures & data

Table 1. Baseline biochemical values (median (25th–75th)).

	Control	Fasting		High fat
n = 9			p Value^a		p Value^b
Post-absorptive glucose (mmol L^−1)	5.1 (4.8–5.1)	4.2 (4.0–4.5)	.01	5.2 (5.1–5.5)	.02
Total Bilirubin (µmol L^−1)	12.0 (6.0–14.5)	30.0 (17.5–38.5)	.01	7.0 (4.0–9.0)	.01
Gamma glutamyltransferase (U L^−1)	15.0 (9.5–16.0)	18 (12.5–21.5)	.04	19.0 (12.5–21.0)	.05
Alkaline Phosphatase (U L^−1)	69.0 (55.5–90.0)	65.0 (59.0–95.0)	.11	79.0 (64.0–97.5)	.02
Free fatty acids, (mmol L^−1)	0.27 (0.17–0.44)	1.05 (0.79–1.41)	.03	0.23 (0.20–0.25)	.92
3-hydroxybutyric acid (mmol L^−1)	0.0 (0.0–0.1)	0.90 (0.65–1.25)	.01	0.0 (0.0–0.1)	1.0
Acetoacetate (mmol L^−1)	0.01(0.01–0.02)	0.23(0.19–0.39)	.01	0.02 (0.01–0.03)	.51
CRP (mg L^−1)	0.5(0.25–1.0)	0.90 (0.30–1.50)	.31	0.40 (0.20–1.10)	.73

^a Fasting vs Control.

^b High-fat diet vs Control.

Figure 1. Example of a plasma concentration time curve in one subject after fasting. Samples were measured by (A) the enzymatic colorimetric assay method or by (B) LC-MS/MS.

Figure 2. Bland–Altman plots of differences between the LC-MS/MS method and the enzymatic colorimetric assay in (A) control samples, (B) after fasting and (C) after a high-fat diet. The dashed line represents the mean difference between the methods, and the dotted line indicates the upper and lower limit of agreement, set to ±2SD of the mean difference.

Figure 3. The median (interquartile range) plasma concentration versus time curve of acetaminophen in three different nutritional conditions. The closed line represents control samples, the dotted line represents fasting samples and the dashed line represents the high-fat diet samples. Concentrations were measured by LC-MS/MS.

Figure 4. Individual AUC_0–8h of acetaminophen in subjects receiving oral dose of 1000 mg acetaminophen after (A) fasting or after (B) a high-fat diet, compared to the AUC_0–8h of acetaminophen after the regular control diet.

Table 2. Pharmacokinetic parameters of acetaminophen in the three different nutritional conditions based on LC-MS/MS measurements.

	Control	Fasting		High-fat diet
n = 9	Median (25th–75th)	Median (25th–75th)	p Value^a	Median (25th–75th)	p Value^b
AUC0–8 (μg/mL*h)	36.4 (35.0–42.8)	43.7 (38.2–46.2)	<.01	42.3 (36.7–44.1)	.44
AUCinf (μg/mL*h)	41.3 (38.1–48.7)	48.9 (43.6–55.3)	<.01	46.1 (40.3–52.5)	.44
T1/2 (h)	2.4 (2.2–2.7)	2.8 (2.5–3.1)	.03	2.4 (2.1–2.6)	.59
Cmax (μg/mL)	16.3 (12.9–22.2)	22.0 (11.2–25.7)	.72	18.9 (11.4–29.5)	.50
Tmax (h)	0.41 (0.25–0.53)	0.30 (0.26–0.89	.52	0.5 (0.3–1.4)	.52
Vd/F ((mg)/(μg/ml))	79.4 (76.8–87.3)	82.6 (69.5–86.7)	.95	77.4 (67.9–85.2)	.59
Cl/F ((mg)/(μg/ml)/h)	24.2 (20.7–26.3)	20.5 (18.1–22.9)	<.01	21.7 (19.1–25.1)	.31

AUC: Area under the curve; T_1/2: plasma half-life; C_max: maximum plasma concentration; T_max: time of maximum plasma concentration; V_d/F: oral volume of distribution; Cl/F: oral clearance.

^a Fasting vs Control.

^b High-fat diet vs Control.