Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid
| Autor: | Soo-Jin Park, Yun Ju Kang, Im-Sook Song, Chul Haeng Lee, Hye Suk Lee, Min-Koo Choi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
rosmarinic acid
Organic anion transporter 1 Pharmaceutical Science lcsh:RS1-441 Pharmacology Article lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine herb-drug interaction Pharmacokinetics medicine 030304 developmental biology 0303 health sciences biology Rosmarinic acid Transporter Drug interaction Probenecid Organic anion-transporting polypeptide organic anion transporter (OAT) chemistry 030220 oncology & carcinogenesis Renal physiology biology.protein pharmacokinetics medicine.drug |
| Zdroj: | Pharmaceutics Volume 13 Issue 1 Pharmaceutics, Vol 13, Iss 83, p 83 (2021) |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13010083 |
| Popis: | We investigated the involvement of drug transporters in the pharmacokinetics of rosmarinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a Km of 26.5 &mu M and a Vmax of 69.0 pmol/min in HEK293 cells overexpressing OAT1, and the plasma concentrations of rosmarinic acid were increased by the co-injection of probenecid because of decreased renal excretion due to OAT1 inhibition. Rosmarinic acid inhibited the transport activities of OAT1, OAT3, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 with IC50 values of 60.6 &mu M, 1.52 &mu M, 74.8 &mu M, and 91.3 &mu M, respectively, and the inhibitory effect of rosmarinic acid on OAT3 transport activity caused an in vivo pharmacokinetic interaction with furosemide by inhibiting its renal excretion and by increasing its plasma concentration. In conclusion, OAT1 and OAT3 are the major transporters that may regulate the pharmacokinetic properties of rosmarinic acid and may cause herb-drug interactions with rosmarinic acid, although their clinical relevance awaits further evaluation. |
| Databáze: | OpenAIRE |
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