Identification of centrally active drugs and herbal constituents as substrates of OATP2B1 and OATP1A2 applying the method of competitive counterflow

Anima Schäfer
as substrates of OATP2B1. Vitexin was also identified as a substrate of OATP1A2 as well as the aglycon apigenin. Mass spectrometric analysis of Passiflora incarnata formulations identified vitexin and orientin, but not apigenin. Consequently, these two constituents could be involved in possible interactions between the formulations and the transporters. Importantly, there is still limited knowledge about systemic availability of flavonoids and to what extent they reach the central nervous
more » ... . However, OATP2B1 is widely considered to be important in intestinal drug absorption, and it follows that constituents of herbal remedies may interact with co-administered oral drugs which are OATP2B1 substrates. Another herbal constituent that we found to interact with OATP2B1 is the St. John's wort constituent hyperforin. It is a potent inhibitor of OATP2B1 function with an IC50 of 0.32 μM and indeed, competitive counterflow experiments identified it as an OATP2B1 substrate. This phloroglucinol is known for drug-herb interactions involving induction of enzymes which mediate drug metabolism. Our finding of OATP2B1 playing a role in cellular uptake of hyperforin suggests that the transporter is a determinant influencing the intracellular effect of the herbal constituent. Furthermore, the identification of hyperforin as an OATP2B1 substrate would imply by extension the plant's interaction potential with OATP2B1 substrates.
doi:10.5451/unibas-ep84877 fatcat:hyen4iavynaabgtcl4ecdgmbfe