Table 2 Linear mixed effects model showing the abundance of annotated metabolites as the response variable while gender, dose, and time remain the independent variables.

	Linear mixed effect model from time 1 to 48 h
		Estimate	Std. error	t. value	p. value
C18(Plasm)-20:4 PE	(Intercept)	1.1003	0.0812	13.5518	–
	Dose	− 0.0890	0.0646	− 1.3779	0.1682
	Gender	− 0.0772	0.0924	− 0.8357	0.4033
	Time*	0.0050	0.0021	2.3691	0.0178
16:1 (DELTA.9-Cis) PC	(Intercept)	1.0554	0.0580	18.2081	–
	Dose*	− 0.1222	0.0593	− 2.0605	0.0393
	Gender	− 0.0483	0.0593	− 0.8144	0.4154
	Time***	0.0061	0.0019	3.2196	0.0013
Methyl γ-linolenate	(Intercept)	0.8299	0.0738	11.2397	–
	Dose*	0.1470	0.0683	2.1523	0.0314
	Gender	− 0.0620	0.0718	− 0.8641	0.3875
	Time*	0.0058	0.0025	2.3286	0.0199
Phosphocholine	(Intercept)	0.8759	0.0706	12.4146	–
	Dose*	0.1693	0.0722	2.3451	0.0190
	Gender	− 0.1060	0.0722	− 1.4681	0.1421
	Time*	0.0052	0.0023	2.2487	0.0245
Palmitamide	(Intercept)	0.8858	0.0746	11.8819	–
	Dose*	0.1642	0.0763	2.1526	0.0314
	Gender	− 0.1167	0.0763	− 1.5296	0.1261
	Time*	0.0053	0.0024	2.1608	0.0307
Oleic acid	(Intercept)	0.8840	0.0695	12.7141	–
	Dose*	0.1532	0.0712	2.1524	0.0314
	Gender	− 0.1035	0.0712	− 1.4552	0.1456
	Time*	0.0048	0.0023	2.1200	0.0340
Oleoyl ethylamide	(Intercept)	0.8499	0.0794	10.6980	–
	Dose*	0.1758	0.0813	2.1619	0.0306
	Gender	− 0.1560	0.0813	− 1.9192	0.0550
	Time***	0.0081	0.0026	3.1088	0.0019
Oleamide	(Intercept)	0.9410	0.1063	8.8523	–
	Dose*	0.3025	0.1088	2.7805	0.0054
	Gender*	− 0.2371	0.1088	− 2.1799	0.0293
	Time*	0.0079	0.0035	2.2814	0.0225

A comprehensive list of all detected features with test statistics (p-value, FDR-adjusted p-value, fold change and log(2) fold change) for each tested group post drug administration compared to pre-drug administration for both tested doses.
Significant values are given in bold.
*Indicates p < 0.05, ** < 0.01, *** < 0.001.

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