Entero-hepatic cycling of methotrexate estimated by use of the D-isomer as a reference marker
Entero-hepatic cycling of methotrexate estimated by use of the D-isomer as a reference marker
复制标题
使用 D 异构体作为参考标记估计甲氨蝶呤的肠肝循环
DOI：
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发表时间：
2004
影响因子：
2.9
通讯作者：
H. Brodthagen
中科院分区：
文献类型：
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作者：
J. Hendel;H. Brodthagen
摘要研究了甲氨蝶呤（L-MTX）光学异构体4-氨基- n10 -甲基翼酰基- d -谷氨酸（D-MTX）的吸收和消除动力学。对9例患者分别给予试验剂量10 mg D-MTX静脉注射和口服，并观察其血药浓度和尿排泄情况。D-MTX静脉注射后血浆曲线呈双指数下降，约16 h后达到零。消除速率常数估计为终端一级速率常数。口服D-MTX的吸收量，通过24小时尿液恢复来估计，在所有病例中都小于给药剂量的3%。由于D-MTX的肠道吸收不显著，因此可以从总体消除速率常数和尿液排出剂量的比例来估计D-MTX的肾脏和胆道分泌率。在3例患者中，获得了D-MTX和L-MTX的消除速率常数。发现这两种化合物的肾清除率几乎相同。D-MTX胆/肾排泄的中位数比值为0.94（范围0.41-1.50），这表明在银屑病治疗剂量水平下，L-MTX有广泛的肠-肝循环和积极的重吸收。
SummaryThe absorption and elimination kinetics of 4-amino-N10-methylpteroyl-D-glutamic acid (D-MTX), the optical isomer of methotrexate (L-MTX), were examined. Test doses of 10 mg D-MTX were administered i.v. and orally to nine patients and its plasma concentration and urinary excretion were followed. The plasma curves after an i.v. bolus injection of D-MTX declined strictly biexponentially and reached zero after about 16 h. The elimination rate constants were estimated as the terminal first order rate constants. The absorption of orally administered D-MTX, estimated by its 24 h urinary recovery, in all cases was less than 3% of the dose administered. The insignificant intestinal absorption made it possible to estimate the renal and biliary secretion rates of D-MTX from the overall elimination rate constant and from the fraction of the dose excreted in urine. In three of the patients, elimination rate constants both for D-MTX and L-MTX were obtained. The renal elimination rates of the two compounds were found to be nearly identical. The median ratio of biliary/renal excretion of D-MTX was 0.94 (range 0.41–1.50), which indicates extensive entero-hepatic cycling and active reabsorption of L-MTX at the therapeutic dose levels used in psoriasis.