Pharmacokinetic Study of Tilianin After Oral Administration in Wistar Rats by HPLC

Tilianin was obtained from the medicinal plant Agastache mexicana (Kunth) Lint & Epling, Lamiaceae, a compound that is candidate to develop new multitarget drug for the treatment of metabolic syndrome–related diseases. The main aim of this work is to determine the pharmacokinetic parameters of tilianin after oral administration in Wistar rats to clarify its absorption pattern, distribution, metabolism, excretion, and permeability. A validated sensitive, selective, and reproducible high-performance liquid chromatography method was developed: r 2 = 0.9992, 5.8 min of retention time, recovery of 100.2%, and LOD and LOQ were 1.86 and 5.63 μg/ml, respectively. By non-compartmental analysis, pharmacokinetic parameters were obtained, such as T max (1.00 h), C max (29.01 μg/ml), T 1/2 (3.33 h), MRT (2.91 h), AUC 0– t (62.25 µg h/ml), AUC 0–∞ (92.47 µg h/ml), K el (0.21 1/h), and Vd/ F (2,788.05 ml). It was also determined that tilianin is deposited at 5 h in the pancreas, liver, and lung. The protonated [M + H] + ion peaks of main metabolites were obtained by LC–MS at m/z 285.1 and 625.2, corresponding to acacetin and tilianin-glucuronic acid conjugation, respectively. In addition, tilianin was not excreted and metabolized through urine. Tilianin had a lower permeability pattern than furosemide and naproxen using everted gut model (1.43 × 10 −6 cm/s). The pharmacokinetic study showed a long-lasting terminal half-life, and rapid absorption of tilianin in rodents. These results support the search to develop tilianin as a new drug for the treatment of metabolic syndrome. Graphical Abstract