Glucuronidation and in vitro interaction of Ginkgo flavonoids with other drugs / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To obtain the information on the glucuronidation of Ginkgo flavonoid and the interaction profile of Ginkgo flavones with other drugs in vitro.</p><p><b>METHODS</b>Ginkgo flavonoids (quercetin, isorhamnetin and keampferol) and other drugs were co-incubated with rat hepatic microsome at 25 degree; the residual concentrations of flavonoids were determined by HPLC. The enzymatic parameters of quercetin, isorhamnetin and keampferol metabolism were assessed. The interactions between flavonoids and these drugs on glucuronidation were observed.</p><p><b>RESULT</b>The K(m) values were ( 24+/-0.05), (148+/-0.09) and (110+/-0.03) micromol/L and the V(max) values were (60+/-0.21), (48+/-0.02) and (34+/-0.02) micromol x g(-1) x min(-1) for quercetin, isorhamnetin and kaempferol, respectively. The IC(50) of nifedipine propafenone ipriflavone and diphenytriazol on flavonoids metabolism were 54 - 70, 69 - 122, 85 - 98 and 210 - 362 micromol, respectively. The inhibition constants (Ki) of diphenytriazol propafenone and ipriflavone on quercetin, isorhamnetin and keampferol metabolism were (57.6, 50.5, 33.1) (33.6, 59.5, 45.2) and(13.7,24.0,15.7) microg/ml respectively. The ratio [I]/[Ki] of the plasma concentration and inhibition constant for propafenone was 0.002 - 0.003.</p><p><b>CONCLUSION</b>The metabolic level of quercetin is the strongest among three Ginkgo flavonoids. Nifedipine propafenone and ipriflavone inhibit the metabolism of quercetin, isorhamnetin and keampferol at different levels. Because of the interaction between Ginkgo flavonoids with nifedipine, caution must be taken when two drugs are used together clinically.</p>