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  • Title: Ex vivo and in vivo investigations of the effects of extracts of Vernonia amygdalina, Carica papaya and Tapinanthus sessilifolius on digoxin transport and pharmacokinetics: assessing the significance on rat intestinal P-glycoprotein efflux.
    Author: Oga EF, Sekine S, Horie T.
    Journal: Drug Metab Pharmacokinet; 2013; 28(4):314-20. PubMed ID: 23291634.
    Abstract:
    Vernonia amygdalina (VA), Carica papaya (CP), and Tapinanthus sessilifolius (ML) are widely used in some countries as medicinal herbs to treat ailments including malaria, cancer, and diabetes. We previously reported the inhibitory effects of these herbs on permeability glycoprotein (P-gp) in Caco-2 cell monolayers. This study used ex vivo and in vivo models to investigate the likelihood of P-gp-mediated herb-drug interactions occurring. The study utilized excised rat intestinal tissues mounted in Ussing chambers to predict changes in drug absorption and an in vivo study in rats using digoxin as the P-gp substrate. Apparent permeability values and pharmacokinetic parameters of digoxin were compared to determine if co-administration of digoxin with ML, CP, or VA modulated the activity of P-gp. When VA was co-administered, the total area under the plasma concentration-time curve was significantly higher (2.1-fold) than when digoxin was administered alone. Co-administration of ML, VA, and CP significantly increased the mean digoxin apparent permeability in the mucosal-to-serosal direction by 7.8, 43.3, and 54.5%, respectively, in comparison to when digoxin was administered alone. These findings suggest that VA increases intestinal absorption of digoxin in vivo by inhibiting P-gp and may also modulate the pharmacokinetic disposition of other p-gp substrate drugs.
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