Comparison of plasma concentrations of the 29 selected endogenous metabolites in cynomolgus monkeys (n = 3) following intravenous administration of PROB alone (40 mg/kg), FSM alone (2 mg/kg), and PROB with FSM

Plasma concentrations of approximately 230 endogenous metabolites were determined by liquid chromatography-mass spectrometry (Supplemental Table 1). Each determination was made in samples collected at 1, 3, and 24 hours postdose from three cynomolgus monkeys, and values for compounds with ≥3.0-fold different plasma concentration at any of three time points in the monkeys treated with PROB and FSM are presented. The P values were determined by paired Student’s t test (Supplemental Table 1).

Metabolite Type and NameRatio of PROB Alone to FSM AloneRatio of PROB with FSM to FSM Alone
C1 hC3 hC24 hC1 hC3 hC24 h
Dicarboxylic acids and derivatives
 C18-di-OH dihydroxyoctadecanoic acid5.
 C18-2 dicarboxylic acid3.
 C20-4 dicarboxylic acid3.
 C18-1 dicarboxylic acid2.
 C16-1 dicarboxylic acid2.
 C12 dicarboxylic acid2.
 C10-1 dicarboxylic acid2.
 C12-1 dicarboxylic acid2.
 C12-OH hydroxydidecanoic acid2.
 C14-1 dicarboxylic acid1.
 Unsaturated tetradecanoyl carnitine (C14-1)
 Unsaturated lauryl carnitine (C12-1)
 Lauryl carnitine (C12)
Small acids produced by gut microflora
 Indole-3 acetic acid8.611.
 Cresol sulfate3.
 Phenyl sulfate3.
 Phenyllactic acid2.
 Indoxyl sulfate2.
Amino acids and derivatives
 Hydroxy-isovaleric acid3.91.54.412.61.86.2
 Aspartic acid2.
 Glucuronic acid8.88.52.610.511.22.4
 Pantothenic acid2.
 Xanthurenic acid3.
 Kynurenic acid3.