Abstract
Herbal drugs are widely used for the auxiliary treatment of diseases. The pharmacokinetics of a drug may be altered when it is coadministered with herbal drugs that can affect drug absorption. The effects of herbal drugs on absorption must be evaluated. In this study, we investigated the effects of Rumex acetosa (R. acetosa) extract on fexofenadine absorption. Fexofenadine was selected as a model drug that is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide 1A2 (OATP1A2). Emodine—the major component of R. acetosa extract—showed P-gp inhibition in vitro and in vivo. Uptake of fexofenadine via OATP1A2 was inhibited by R. acetosa extract in OATP1A2 transfected cells. A pharmacokinetic study showed that the area under the plasma concentration–time curve (AUC) of fexofenadine was smaller in the R. acetosa extract coadministered group than in the control group. R. acetosa extract also decreased aqueous solubility of fexofenadine HCl. The results of this study suggest that R. acetosa extract could inhibit the absorption of certain drugs via intervention in the aqueous solubility and the drug transporters. Therefore, R. acetosa extract may cause drug interactions when coadministered with substrates of drug transporters and poorly water-soluble drugs, although further clinical studies are needed.
Highlights
Oral drug administration is a preferred route, offering the advantages of convenience and safety
This study investigated the effects of Rumex acetosa (R. acetosa) extract on P-gp and organic anion transporting polypeptide 1A2 (OATP1A2) in vitro and on fexofenadine absorption in vivo
It indicates that the inhibitory effect of R. acetosa on fexofenadine uptake discussed in Section 3.2 was not due to the cytotoxic effects of R. acetosa on HEK293 cells at the concentration range tested
Summary
Oral drug administration is a preferred route, offering the advantages of convenience and safety. Many drug interactions with foods and other drugs occur via alteration of drug absorption. It is necessary to investigate possible interactions mediated by transporters that could alter systemic exposure of drugs. Drug–drug interactions may occur when substrates of P-gp (e.g., cimetidine, digoxin, doxorubicin, fexofenadine, and vinblastine) are coadministered with inhibitors of P-gp (e.g., atorvastatin, ketoconazole and quinidine) or inducers of P-gp (e.g., rifampin and clotrimazole) [7,8]. The OATP family is an important transporter for drug disposition. The OATP members of the solute carrier (SLC) family, contributes to the uptake of substrates, including endogenous compounds and drugs [9,10]. Given that St. John’s wort was found to increase P-gp expression [13], it is necessary to evaluate the effects of herbal supplements on these transporters. Despite the widespread use of herbal drugs in combination with drugs, there has been little research on the interactions between drugs and herbal medicines
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