title: Interaction between ticlopidine or warfarin or cardioaspirin with a highly standardized deterpened Ginkgo biloba extract (VR456) in rat and human.
abstract: Ginkgo biloba is available in Europe as an over-the-counter drug and it is reported to cause hemorrhage when co-administered with other anti-platelet agents. We set out to study the interactions of ticlopidine with Ginkgo biloba extract or VR456, a new highly standardized deterpened extract from Ginkgo biloba leaves. Male Wistar rats were used to study the effects of ticlopidine (50-100 mg/kg/day), given alone and in combination for 5 days with Ginkgo biloba extract (50 mg/kg/day) or VR456 (50 mg/kg/day), on bleeding time and ex vivo ADP-induced platelet aggregation measurements. In addition, human studies were performed with the compounds under investigation. Combined treatment of ticlopidine and undeterpened Ginkgo biloba extract increased anti-platelet effect and prolonged the bleeding time in the rat. On the contrary, the combination treatment of ticlopidine and VR456 increased anti-platelet effect but did not prolong bleeding time. Moreover, daily administration of 360 mg of VR456 for 14 days to ticlopidine-treated humans did not highlight any unwanted effect and did not alter PT/INR and PTT parameters. Same results have been also obtained in warfarin or in cardioaspirin-treated patients. These data point out the clear role played by the terpenoid, PAF-antagonist fraction of Ginkgo biloba extract in affecting bleeding risk in anticoagulant-treated subjects and suggest VR456 as a possible option treatment in geriatric people subjected to anticoagulant treatment where the use of standard Ginkgo biloba extracts are discouraged.
authors.affiliation: Scientific Department, Velleja Research, Pontenure, Piacenza, Italy. f.dipierro@vellejaresearch.com
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Pierro
authors.forename: Francesco
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Lucarelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossoni
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001794:Blood Pressure; D004347:Drug Interactions; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D006339:Heart Rate; D006470:Hemorrhage / Q000139:chemically induced; D019934:International Normalized Ratio; D008297:Male; D010314:Partial Thromboplastin Time; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D018515:Plant Leaves; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013988:Ticlopidine / Q000494:pharmacology*; D014859:Warfarin / Q000494:pharmacology*; D000096983:Ginkgo Extract
chemical_list: D001241:Aspirin; D046934:Ginkgolides; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine; D014859:Warfarin; C572201:Ginkgo biloba extract VR456; D000096983:Ginkgo Extract