Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

Lei, He-Ping; Guo, Wei; Wang, Liansheng; Ouyang, Dongsheng; Chen, Hao; Li, Qing; Zhang, Wei; Tan, Zhi‐Rong; Li, Fan; He, Yijing; Zhou, Hong‐Hao

doi:10.1345/aph.1l537

Cited by 37 publications

(26 citation statements)

References 23 publications

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“…The impact of CYP2C19 genetic variants on voriconazole pharmacokinetics has been confirmed and characterized in a number studies in adult healthy volunteers (Table 2) [7,8,76–80]. Pharmacokinetic parameters including half-life (t 1/2 ) and AUC are significantly increased in CYP2C19 PM compared to CYP2C19 EM receiving oral voriconazole.…”

Section: Voriconazole Pharmacokinetics and Cyp2c19 Polymorphismsmentioning

confidence: 88%

Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole

Moriyama

Kadri

Henning

et al. 2015

Curr Fungal Infect Rep

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Voriconazole is an antifungal triazole that is the first line agent for treatment of invasive aspergillosis. It is metabolized by CYP2C19, CYP2C9, and CYP3A4 and demonstrates wide interpatient variability in serum concentrations. Polymorphisms in CYP2C19 contribute to variability in voriconazole pharmacokinetics. Here, evidence is examined for the use of voriconazole therapeutic drug monitoring (TDM) and the role of CYP2C19 genotyping in voriconazole dosing. The majority of studies exploring the impact of voriconazole TDM on efficacy and safety have found TDM to be beneficial. However, most of these studies are observational, with only one being a randomized controlled trial. High-volume multicenter randomized controlled trials of TDM are currently not available to support definitive guidelines. There is a significant relationship in healthy volunteers between CYP2C19 genotype and voriconazole pharmacokinetics, but this association is markedly less visible in actual patients. While CYP2C19 genotype data may explain variability of voriconazole serum levels, they alone are not sufficient to guide initial dosing. The timeliness of availability of CYP2C19 genotype data in treatment of individual patients also remains challenging. Additional studies are needed before implementation of CYP2C19 genotyping for voriconazole dosing into routine clinical care.

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Section: Voriconazole Pharmacokinetics and Cyp2c19 Polymorphismsmentioning

confidence: 88%

Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole

Moriyama

Kadri

Henning

et al. 2015

Curr Fungal Infect Rep

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“…At 0.25 h after administration, GK was detected at the highest concentration in all of these tissues, while it was generally cleared from all of these tissues at 4 h. Besides, liver showed significantly higher levels of GK exposure, followed by kidney, heart, and spleen in that order, which may be attributed to the blood flow in these organs. Recently, ginkgo has been reported to have multiple interaction with other drugs base on the influence of CYP2C19 [30], the accumulation of GK on liver indicated that it was also important to concern the interaction between GK and co-administrated drugs. In addition, the concentration of GK in the brain was extremely low, suggesting that GK was difficult to cross the blood-brain barrier of normal rats, this may due to the p-gp efflux accompanied by the para-cellular pathway for passive diffusion [31].…”

Section: Tissue Distribution Studymentioning

confidence: 99%

Pharmacokinetic studies of ginkgolide K in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry

Fan

Liu

Guo

et al. 2015

Journal of Chromatography B

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Ginkgolide K (GK), a derivative compound of ginkgolide B, has been recently isolated from the leaves of Ginkgo biloba. It is a powerful natural platelet activate factor (PAF) antagonist, and also has obvious protect effects for cerebral ischemia. However, no reports have been described for the pharmacokinetic study of GK. In this study, a simple, sensitive and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of GK in rat plasma and tissues. Biological samples were pretreated by an efficient liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved on an Agilent ZORBAX SB-Aq column (4.6 mm × 50 mm, 1.8 μm) with a mobile phase of 0.5% aqueous formic acid (A)-menthol (B). Quantitation was carried out on a triple quadruple mass spectrometry using positive electrospray ionization in multiple reaction monitoring mode. Diazepam was used as internal standard (IS). The ion transitions monitored were set at m/z 407.10 → 389.20 and m/z 285.08 → 193.10 for GK and IS, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of GK after intravenous administration. The current results have indicated that pharmacokinetic parameters of GK vary in a dose-dependent manner with rapid elimination in 4h. The major distribution tissues of GK in rats were liver and kidney. This study would provide critical information to promote the future study of GK.

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“…Ginkgo biloba is generally considered safe and well tolerated in the general population, however, it may induce drug interactions [22]. Human studies have found no significant effect for ginkgo biloba on cytochromes 2B6, 2C19 or 2C9 and a study of elderly volunteers found no significant effect on CYP3A4 although the herb does appear to induce CYP3A in young volunteers [37][38][39][40][41]. Several case reports have suggested a link between ginkgo biloba ingestion and haemorrhage, however, the reliability of these cases is questionable as several clinical studies found no significant effects on bleeding with ginkgo ingestion [27][28][29][30][31][32][33][34][35][36].…”

Section: The Quality Control Regulation Of Complementary Medicine Promentioning

confidence: 99%

Use of Complementary Medicines by Cardiac Surgery Patients; Undisclosed and Undetected

Braun

Cohen

2011

Heart, Lung and Circulation

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Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

Cited by 37 publications

References 23 publications

Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole

Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole

Pharmacokinetic studies of ginkgolide K in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry

Use of Complementary Medicines by Cardiac Surgery Patients; Undisclosed and Undetected

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