In vitro and in vivo assessment of herb drug interactions

Venkataramanan, Raman; Komoroski, Bernard J.; Strom, Stephen C.

doi:10.1016/j.lfs.2005.12.021

Cited by 100 publications

(65 citation statements)

References 66 publications

(67 reference statements)

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Section: Discussionmentioning

confidence: 99%

Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review

Tsai

Lin

Pickard

et al. 2012

International Journal of Clinical Practice

150

112

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Summary Background and Aims: The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. This review aims to evaluate the documented HDS‐drug interactions and contraindications. Methods: A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet. Results: While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS‐drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John’s Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS‐drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal/genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications. Conclusions: Although HDS‐drug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS‐drug interactions and contraindications. The findings would facilitate the health‐care professionals to communicate these documented interactions and contraindications to their patients and/or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review

Tsai

Lin

Pickard

et al. 2012

International Journal of Clinical Practice

150

112

View full text Add to dashboard Cite

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“…However, limited data exist for phase 2 metabolic pathways and the role of transporters in vivo (Venkataramanan et al, 2006). Silymarin metabolism in vivo may have a role in herbal-drug interactions, especially as doses for silymarin are increased.…”

Section: Discussionmentioning

confidence: 99%

“…Using the sum of six flavonolignans as the total content of silymarin, the measured contents of silymarin ranged from 57 to 71%. Standardized milk thistle extracts are generally considered to contain approximately 70 to 80% as silymarin (Flora et al, 1998;Simánek et al, 2000;Jacobs et al, 2002;Venkataramanan et al, 2006), whereas the content of silybin (SB A ϩ SB B ) represents approximately 40 to 70% of the total amounts of silymarin (Jacobs et al, 2002;USP, 2006;Venkataramanan et al, 2006). As shown in Table 1, the relative percentages of silybin (SB A ϩ SB B ) were found to be 48 to 56% in standardized milk thistle extracts (Sigma-Aldrich and USP) and 54 to 57% in commercial milk thistle tablets and capsules.…”

Section: Estimation Of Silymarin Flavonolignans In Milkmentioning

confidence: 99%

Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract

Zhao

Dumas

Schrieber³

et al. 2007

Drug Metab Dispos

155

156

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ABSTRACT:Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB B ), isosilybin A (ISB A ), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg of standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1-3 and 3-8 h for free and conjugated, respectively). The AUC 03ؕ values of the conjugated silymarin flavonolignans were 4-to 30-fold higher than those of their free fractions, with SB B (mean AUC 03ؕ ‫؍‬ 51 and 597 g ⅐ h/l for free and conjugated, respectively) and ISB A (mean AUC 03ؕ ‫؍‬ 30 and 734 g ⅐ h/l for free and conjugated, respectively) exhibiting higher AUC 03ؕ values in comparison with other flavonolignans. Near the plasma peak times (1-3 h), the free, sulfated, and glucuronidated flavonolignans represented approximately 17, 28, and 55% of the total silymarin, respectively. In addition, the individual silymarin flavonolignans exhibited quite different plasma profiles for both the free and conjugated fractions. These data suggest that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma.

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“…Bifendate is a synthetic intermediate of schisandrin, which is also a component of the indigenous Chinese plant Wu Wei Zi. It has been shown that many herbal products have the ability to directly alter hepatic drug metabolizing enzymes, such as CYPs, and interact with co-administered drugs, especially drugs that can function as hepatoprotective, detoxifying, and antioxidative agents [39] . For example, Gan Cao (licorice root) can increase serum CYP levels and the metabolic rate of imipramine.…”

Section: Discussionmentioning

confidence: 99%

Effect of bifendate on the pharmacokinetics of cyclosporine in relation to the CYP3A4*18B genotype in healthy subjects

Zeng

et al. 2009

Acta Pharmacol Sin

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Aim:To evaluate the potential drug-drug interactions between bifendate and cyclosporine, a substrate of CYP3A4, in relation to different CYP3A4*18B genotype groups. Methods: Eighteen unrelated healthy subjects (six CYP3A4*1*1, six CYP3A4*1/*18B, and six CYP3A4*18/*18B) were selected for this study. After repeated oral administration of a placebo or bifendate (three times daily for 14 d), the wholeblood level of cyclosporine was measured using high performance liquid chromatography-electrospray mass spectrometry (HPLC/ESI-MS). This study was carried out in a two-phase randomized crossover manner. Results: After the treatment with bifendate, the areas under the curve (AUC 0-24 and AUC 0-∞ ) decreased significantly by 9.7%±3.7% (P=0.01) and 19.2%±16.8% (P=0.001) in CYP3A4*1/*1 subjects, 11.3%±9.4% (P=0.03) and 10.5%±9.6% (P=0.043) in CYP3A4*1/*18B subjects, and 40.2%±14.7% (P=0.02) and 37.5%±15.8% (P=0.003) in CYP3A4*18B/*18B subjects. Meanwhile, the decreases in the AUC 0-24 and AUC 0-∞ values in the three groups were significantly different (using one-way analysis of variance, P=0.001 and P=0.001), and the change in the CYP3A4*18B/*18B group was greater than that in the other two groups. The oral clearance of cyclosporine was altered in all the subjects, with substantial increases by 10.2%±4.4% (P=0.004) in CYP3A4*1/*1 subjects, 14.0%±12.0% (P=0.048) in CYP3A4*1/*18B subjects, and 32.4%±21.7% (P=0.013) in CYP3A4*18B/*18B subjects. Conclusion: These results suggest that bifendate decreases the plasma concentration of cyclosporine in a CYP3A4 genotypedependent manner.

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In vitro and in vivo assessment of herb drug interactions

Cited by 100 publications

References 66 publications

Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review

Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review

Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract

Effect of bifendate on the pharmacokinetics of cyclosporine in relation to the CYP3A4*18B genotype in healthy subjects

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