Pharmacokinetics and Tissue Distribution of (13)C-Labeled Succinic Acid in Mice

Succinic acid is widely used as a food additive, and its effects on sepsis, cancer, ataxia, and obesity were recently reported. Dietary drug exposure studies have been conducted to evaluate the in vivo efficacy of succinic acid, but limited pharmacokinetic information is available. Therefore, this study evaluated the pharmacokinetic profiles and tissue distribution of succinic acid following a single intravenous or oral dose. A surrogate analyte, succinic acid-(13)C(4) ((13)C(4)SA), was administrated to distinguish endogenous and exogenous succinic acid. The concentration of (13)C(4)SA was determined by a validated analytical method using mass spectrometry. After a 10 mg/kg intravenous dose, non-compartmental pharmacokinetic analysis in plasma illustrated that the clearance, volume of distribution, and terminal half-life of (13)C(4)SA were 4574.5 mL/h/kg, 520.8 mL/kg, and 0.56 h, respectively. Oral (13)C(4)SA was absorbed and distributed quickly (bioavailability, 1.5%) at a dose of 100 mg/kg. In addition, (13)C(4)SA exposure was the highest in the liver, followed by brown adipose tissue, white adipose tissue, and the kidneys. This is the first report on the pharmacokinetics of succinic acid after a single dose in mice, and these results could provide a foundation for selecting dosing regimens for efficacy studies.