Study On Drug Interactions Of Ginkgo Biloba Extract And Cilostazol

For an oral herbal medicine,Ginkgo biloba extract(GBE)is well-known by all of us. Cilostazol is an anti-platelet medicine used in clinical.Both of GBE and cilostazol were metabolited by CYP3A4 and CYP2C19,the possibility of drug-drug interaction were expected.The signs and symptoms of interaction might be hemorrhage,bleeding and so on. After searching the European patent office,we found that anti-platelet medicine such as ticlopidine,dipyridamole,aspirin were comprised with GBE as a pharmaceutical compound. GBE and cilostazol can be an anti-angiogenic composition in clinical use.The study of mechanisms of drug interactions is of much value in selecting the drug combinations to provide rational therapy.The drug interaction studies assume much importance especially for drugs that have risk to experience some side effects and have narrow margin of safety.Quilibrium dialysis and HPLC were employed to measure the concentration of cilostazol. Results show that under four concentration(0.4,0.8,1.2,1.6μg·mL^-1of drug,the protein-binding rates of cilostazol alone were 95.7%,94.9%,94.8%,94.3%;when together with GBE,the protein-binding rates of cilostazol were 95.0%,93.9%,93.6%,91.8%, respectively.Therefore,the protein-binding rate of cilostazol was not disturbed by GBE.Rat cytochrome P450 enzymes offer possibilities for identification of enzymes involved in metabolic reactions and for kinetic characterization of the reactions.A method of assaying the influence of GBE on cilostazol in rat cytochrome P450 enzymes was developed.We obtained IC₅₀to estimate weather GBE had strong inhibitions on cilostazol or not.Then we calculated K_i to make sure the risk degree of drug interaction in vivo.The results showed that the K_m and V_maxdiffered between each groups of microsomes.Most importantly,GBE exhibited a mediate inhibition of the activity of P450 microsomes.It was suggested that GBE and cilostazol might cause a drug-drug interaction in clinical use.The effect of GBE on the pharmacokinetics of cilostazol in Beagle dogs in randomized, single dose,two-way cross over was studied.Cilostazol was administered following a consecutive seven-day taking of GBE 400mg a day or standardizes foods.The plasma concentrations of cilostazol were determined by a validated HPLC method that entailed ultraviolet detection.The 90%CI for C_maxof cilostazol were in the predefined 0.7-1.43 region, the 90%CI for AUC_0-tand AUC_0-∞were overlapped bur ranged to the outside of the predefined 0.8-1.25 region.The platelet aggregation rates were measured after the blood samples were obtained using a whole blood platelet aggregometer.The maximum inhibiton of platelet aggregation without GBE was 46.2%±8.56%,and the maximum inhibiton of platelet aggregation with GBE was 68.66%±4.17%,respectively.Our study witnessed a rapid,high effect action in combination of cilostazol and GBE.