Methotrexate (MTX) is an important immunosuppressant with narrow therapeutic index. The transport of MTX was associated with MRP 1, MRP 2, MRP 3 and MRP 4. Our previous studies supported by CCMP indicated that coadministration of polyphenol-rich herbs including Dahuang, Huangchin, Sanhuang-Sheishin Tang and Gergen-Chinlien Tang resulted in the systemic exposure and residence time of MTX, which led to increased mortality of rats. In general practice of drug information consultation, the patients are suggested to take Chinese medicine at 2 hour after the administration of western medicine. Whether this way of combined therapy is safe or not await further study. This project attempts to administer MTX and then administered Chinese herbs including Dahuang, Huangchin, Sanhuang-Sheishin Tang and Gergen-Chinlien Tang at 1.5 and 3 h after MTX dosing. The pharmacokinetic parameters of MTX will be compared with those after dosing with MTX alone. The blood samples will be collected via cardiopuncture and the concentrations of MTX will be determined using FPIA method. The pharmacokinetic parameters will be calculates using noncompartment model of WINNONLIN and compared statistically using ANOVA. This study will provide useful information for the efficacy and safety of MTX in clinical use.
