Pharmacokinetics of ginkgolides A, B and K after single and multiple intravenous infusions and their interactions with midazolam in healthy Chinese male subjects.
Purpose: Ginkgo terpene lactones meglumine injection (GMI) is a novel preparation of traditional Chinese medicine that contains ginkgolides A, B and K (GA, GB, GK, respectively) as its primary components. In this study we evaluated the safety, tolerability and pharmacokinetics of these three ginkgol...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 73; no. 5; pp. 537 - 547 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | clinical trial pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
May2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=122987772&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 122987772 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2017 vid: 73 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 122987772 122987772 143991304 122987772 10.1007/s00228-017-2197-3 122987772 ppf: 537 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Pharmacokinetics of ginkgolides A, B and K after single and multiple intravenous infusions and their interactions with midazolam in healthy Chinese male subjects. aug: au: Shao, Feng Zhang, Hongwen Xie, Lijun Chen, Juan Zhou, Sufeng Zhang, Jinsong Lv, Jinru Hao, Weiwen Ma, Yunsu Liu, Yun Ou, Ning Xiao, Wei affil: Phase I Clinical Trial Unit , First Affiliated Hospital-Nanjing Medical University , Nanjing 210029 China sug: subj: Ginkgo Biloba Pharmacokinetics Infusions, Intravenous Midazolam Drug Interactions Human Chinese Persons Male Research Methodology Clinical Trials Male ab: Purpose: Ginkgo terpene lactones meglumine injection (GMI) is a novel preparation of traditional Chinese medicine that contains ginkgolides A, B and K (GA, GB, GK, respectively) as its primary components. In this study we evaluated the safety, tolerability and pharmacokinetics of these three ginkgolides after single and multiple intravenous infusions of GMI. We also investigated the effect of GMI on cytochrome P450 3A4 (CYP3A4) in healthy Chinese volunteers. Methods: In this open-label, placebo-controlled study 15 subjects were randomly assigned to receive GMI or matched placebo (4:1 ratio). All subjects first received midazolam (MDZ) on day 1, followed by a 6-day washout. On Day 8, the subjects were started on once-daily dosing of either GMI or placebo for 14 days. Lastly, on Day 22 the subjects were given second dose of MDZ + GMI or MDZ + placebo. Plasma concentrations of ginkgolides, MDZ and its metabolite 1-hydroxy midazolam were quantified. Results: The steady-state conditions of GA, GB and GK were achieved after 6 days of daily dosing. Following a single dose of GMI (Day 8) the area under the concentration-timecurve from zero to 24 h after administration (AUC) of GA, GB and GK (arithmetic ± standard deviation) was 4.10 ± 1.06, 4.61 ± 1.31 and 0.127 ± 0.102 h μg/mL, respectively; the corresponding values following multiple doses of GMI (Day 19) were 3.94 ± 1.16, 5.00 ± 1.55 and 0.118 ± 0.096 h μg/mL, respectively. The mean accumulation ratios were 0.95, 1.08 and 0.89 for GA, GB and GK, respectively. Additionally, the geometric mean [peak concentration (C) and AUC] ratios of MDZ and 1-hydroxy midazolam were all within the specified acceptance ranges in the MDZ + placebo treatment and MDZ + GMI treatment. Conclusions: Our results show that GMI was well tolerated during the entire study. There was no systemic accumulation and no significant effects on the pharmacokinetics of MDZ in healthy Chinese male subjects after repeated dosing of GMI. pubtype: Academic Journal doctype: clinical trial pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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