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Smilax glabra Rhizoma affects the pharmacokinetics and tissue distribution of methotrexate by increasing the P‑glycoprotein mRNA expression in rats after oral administration.

Methotrexate (MTX) is a widely used immunosuppressant and anticancer agent with high toxicity. Smilax glabra Rhizoma (SGR) has the effect of detoxification and immunoregulation, and has been used as both food and folk medicine in many countries. Co‑administration of MTX and SGR occurs in several diseases. However, whether they work synergistically or are incompatible remains unknown. In the present study, MTX was administrated to rats alone or combined with SGR. Blood and tissue samples were collected at designated times. The concentrations of MTX were determined by high‑performance liquid chromatography. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detected the gene expression. SGR decreased the AUC0‑t and Cmax of MTX by 44.5 and 48.2%, but in a tissue‑dependent manner. The total exposure of MTX was significantly decreased in the small intestine, stomach, plasma, and kidney by 61.6, 34.7, 63.3 and 46.1%, respectively, but was increased in the lung and spleen by 82.9 and 21.0%, respectively. RT‑qPCR demonstrated that SGR increased the mean P‑glycoprotein (gp) mRNA expression in the small intestine 2.54 times, but had a marginal effect on the expression of organic anion transporting polypeptide 2, and organic anion transporter (OAT)1 and OAT2. These results suggested that SGR affects the pharmacokinetics of MTX in a tissue‑dependent manner by affecting P‑gp, and the clinical effect of co‑administration depended on the disease site.