Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112, Japan.
Pharmaceuticals (Basel). 2012 Aug 10;5(8):802-36. doi: 10.3390/ph5080802.
Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX) is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.
米佐菌胺经口服给药，在体内不代谢即排泄至尿液中。许多研究小组报告了米佐菌胺剂量与血清峰浓度、剂量与 AUC 以及 AUC 与米佐菌胺累积尿排泄之间的线性关系。相反，米佐菌胺的口服生物利用度存在显著的个体间变异性，而个体内变异性较小。米佐菌胺的个体间变异性主要被认为是由于转运体基因的多态性所致。甲氨蝶呤（MTX）根据剂量口服和/或通过肠外途径给药。代谢酶和多种转运体参与 MTX 的药代动力学。MTX 的口服生物利用度表现出明显的个体间变异性，并随 MTX 剂量的增加而饱和，个体内变异性较小，提示转运体和酶的基因多态性有一定作用。米佐菌胺和 MTX 的治疗药物监测有望提高它们在类风湿关节炎治疗中的临床疗效。
