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The Potential Drug–Drug Interactions of Ginkgolide B Mediated by Renal Transporters
Author(s) -
Qiu Zhixia,
Wang Lei,
Dai Yu,
Ren Weichao,
Jiang Wenwen,
Chen Xijing,
Li Ning
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5294
Subject(s) - probenecid , organic anion transporter 1 , renal physiology , excretion , pharmacology , chemistry , transporter , drug , organic cation transport proteins , kidney , renal function , medicine , endocrinology , biochemistry , gene
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. Copyright © 2015 John Wiley & Sons, Ltd.