title: The potential drug-drug interactions of ginkgolide B mediated by renal transporters.
abstract: Ginkgolide B (GB) is a selective and strong antagonist of platelet-activating factor with great benefits in CNS diseases treatment. The renal excretion constitutes the predominant secretory pathway of GB. Here, we investigated the potential role of renal drug transporters in GB urinary excretion. The intravenous administration of GB was conducted at 10 min post-administration of probenecid (potential inhibitor of organic anion transporters/organic anion transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi-drug resistance proteins) in rats. Pretreated with probenecid, the systemic exposure of GB was significantly elevated from 8.319 ± 1.646 to 14.75 ± 1.328 µg · mL(-1) ∙h but with reduced total clearance from 1.17 ± 0.331 to 0.596 ± 0.0573 L · h(-1) ∙kg(-1) accompanying no changes in plasma elimination half-lives compared with control group. With no pronounced effect on metabolic elimination, the decreased total clearance was closely pertained to the reduced renal excretion, indicating the potential effect of organic anion transporters and/or organic anion transporting polypeptides in renal secretory of GB from blood to urine. However, the possible effect of bromosulfophthalein was restricted within a minor extent, suggesting the mild role of multi-drug resistance protein in GB renal excretion.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Qiu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.forename: Weichao
authors.initials: W
authors.lastname: Ren
authors.forename: Wenwen
authors.initials: W
authors.lastname: Jiang
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000818:Animals; D004347:Drug Interactions; D046934:Ginkgolides / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects*; D007783:Lactones / Q000493:pharmacokinetics*; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors; D011339:Probenecid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013448:Sulfobromophthalein / Q000494:pharmacology*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D046934:Ginkgolides; D007783:Lactones; D027361:Organic Anion Transporters; D013448:Sulfobromophthalein; C045856:ginkgolide B; D011339:Probenecid
keywords: Ginkgolide B; drug-drug interactions; renal drug transporters; renal excretion