抗壞血酸對藥物運輸蛋白 - P-gp與代謝酵素 - CYP 3A4之影響

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抗壞血酸對藥物運輸蛋白 - P-gp與代謝酵素 - CYP 3A4之影響

Effects of Ascorbic Acid on Drug Transporters – P-gp and Metabolic Enzyme – CYP 3A4

鄭翰緯 , Masters　　Advisor：李珮端　　Co-advisor ：侯鈺琪;蔡尚元

繁體中文

抗壞血酸； P-glycoprotein ； CYP 3A4 ； Ascorbic acid ； P-glycoprotein ； CYP 3A4

Abstract │ Reference (79) │ Altmetrics

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Ascorbic acid, one of the essential vitamins for human body, is widely distributed in many natural fruits and vegetables. It is a common dietary supplement that is not uncommon in chronic patients. Therefore, the benefits or risk of the combined use of ascorbic acid with medicines warrants investigation.
Cyclosporine (CsA) is an immunosuppressant clinically used to prevent rejection of allograft organ or for the treatment of autoimmune diseases. Tamoxifen (TAM) is an estrogen antagonist clinically used for the treatment of estrogen receptor positive breast cancer. Both CsA and TAM have been reported as substrates of P-glycoprotein (P-gp) and CYP 3A4. In this study, CsA and TAM were used as probe drugs to investigate the effect of ascorbic acid on P-gp and CYP 3A4.
Rats were administrated CsA or TAM alone and coadministrated with single or multiple doses of ascorbic acid. Blood samples were collected at predetermined time points. The blood concentrations of CsA were determined by fluorescence polarization immunoassay. TAM and its metabolites were analyzed by LC-MS method.
The results showed that coadministration with single dose of ascorbic acid significantly decreased the AUC and Cmax of CsA by 79.5 % and 72.4 %, and mutiple doses of ascorbic acid decreased the AUC and Cmax of CsA by 77.2 % and 65.3 % respectively. However, coadministration of ascorbic acid did not significantly alter the pharmacokinetics of TAM. Mechanism studies showed that ascorbic acid activated the efflux function of P-gp, but did not affect the activity of CYP 3A4.
In conclusion, ascorbic acid is an activator of P-gp, but not a modulator of CYP 3A4.

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