Wang Z H, Yu Z L
Department of Pediatrics, First Teaching Hospital, Beijing Medical University.
Chin Med J (Engl). 1992 Feb;105(2):147-52.
This study was undertaken to research the pharmacokinetics and bioavailability of methotrexate (MTX). Plasma concentrations were measured by fluorescent spectrometry in 20 normal SD rats, and 28 measurements were done in children with acute lymphoblastic leukemia (ALL). Both rats and children were divided into four groups. Either 20 mg/m2 or 40 mg/m2 of MTX was given IV or PO in each group. The plasma MTX concentrations were measured within 8 hours after administration. The concentration versus time curves were fitted by MCPKP program for pharmacokinetics (PK) and the parameters calculated. After PO administration, the peak concentration, duration of therapeutic concentration and bioavailability were much lower than that after IV administration. The differences were more obvious at 40 mg/m2 dosage. The higher the PO dosage, the lower the bioavailability. Absorption of PO MTX in children with ALL varied widely and uniform concentration was not expected even after equal dosage. Drug concentration was not necessarily increased with dosage. It is our conclusion that drug concentrations and PK parameters should be measured in patients receiving PO MTX therapy.
本研究旨在探讨甲氨蝶呤（MTX）的药代动力学和生物利用度。采用荧光光谱法测定了20只正常SD大鼠的血浆浓度，并对28例急性淋巴细胞白血病（ALL）患儿进行了测定。大鼠和患儿均分为四组。每组分别静脉注射或口服20mg/m²或40mg/m²的MTX。给药后8小时内测定血浆MTX浓度。用MCPKP程序拟合浓度-时间曲线以进行药代动力学（PK）分析并计算参数。口服给药后，峰浓度、治疗浓度持续时间和生物利用度均远低于静脉给药后。在40mg/m²剂量时差异更明显。口服剂量越高，生物利用度越低。ALL患儿口服MTX的吸收差异很大，即使剂量相同也无法预期达到均匀浓度。药物浓度不一定随剂量增加。我们的结论是，接受口服MTX治疗的患者应测定药物浓度和PK参数。
