Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John's wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I), three were estimated as probable (level II), and ten and twenty-one were possible (level III) and doubtful (level IV), respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes.

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Abstract:There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography-mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and C max of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects.This study aimed to support a generic consistency evaluation program,initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the withinsubject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population.

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Puerarin increased warfarin metabolism and offset warfarin anticoagulation by inducing rCyps, upregulating VKOR and inhibiting thrombomodulin in rats. The clinical impact of such potential interactions warrants further verification. Copyright © 2016 John Wiley & Sons, Ltd.

The roxithromycin, macrolide antibiotics, is recommended for treating mycoplasma infection and has the potential to be administered to pregnant women who are susceptible to the infection. This study compared the pharmacokinetic properties and tissue distribution of roxithromycin among pregnant mice and their foetuses. We also determined the level of CYP3A1, a major enzyme for roxithromycin metabolism, in liver microsomes and investigated the placental transport properties of roxithromycin. Biosamples were collected from female mice at gestational day 17 after a single intragastric administration of roxithromycin. A sensitive and specific liquid chromatography-tandem mass spectroscopy method was developed to detect the drug concentration and to obtain kinetic data. The level of CYP3A1 was significantly lower in foetal liver compared with that in maternal liver according to Western blot data, suggesting a decreased metabolism and prolonged half-life of roxithromycin in the foetus. The tissue distributions of roxithromycin were similar between mother and foetus, indicating that the placental barrier did not block the transport of roxithromycin from mother to foetus. The current findings are consistent with the clinical efficacy of roxithromycin in both pregnant mothers and foetuses. Based on this study, it is feasible and reasonable to predict the transport properties of other lipophilic drugs during pregnancy.

CBG inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of SAL in hypoxic rats.