Rapid pharmacokinetic characteristic evaluation of scutellarin derivatives in vitro / 中国药理学通报

ABSTRACT

Aim To study the pharmacokinetic char-acteristics of serial compounds that took the scutellarin and scutellarein as lead compounds by using the model of in vitro liver microsomes, and to screen compounds whose medicinal properties were superior to scutellarin and scutellarein. Methods The content of candidate compounds at different times by incubation system of rat liver microsome was determined using UPLC-MS/MS method. Candidate compounds that contained opti-mum T1/2 and CLint were screened. Enzyme kinetics and conversions of candidate compounds were com-pared with those of scutellarin and scutellarein. Re-sults The T1/2 and CLint were optimum of W11 com-pared with those of scutellarin and scutellarein; the Vmax, Km and CLint of compound W11 were (10.25 ±2.59 ) μmol · min-1 · g-1 , ( 4.64 ±0.24 ) μmol · L-1 and ( 2.29 ±0.23 ) L · min-1 · g-1; the Vmax , Km and CLint of scutellarin were (45.95±9.50) μmol · min-1 · g-1 , ( 10.19 ± 1.66 ) μmol · L-1 and (4.48±0.20) L·min-1 ·g-1; W11 might be me-tabolized into scutellarin and M1 ( a compound with mo-lecular weight of 577 after demethylating ) . Conclu-sion The pharmacokinetic properties of candidate compound W11 are better than those of scutellarin, and it could release scutellarin.