THE PHARMACOKINETICS OF METHOTREXATE AND ITS 7-HYDROXY METABOLITE IN PATIENTS WITH RHEUMATOID-ARTHRITIS
THE PHARMACOKINETICS OF METHOTREXATE AND ITS 7-HYDROXY METABOLITE IN PATIENTS WITH RHEUMATOID-ARTHRITIS
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DOI：
10.1111/j.1365-2125.1993.tb04158.x
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发表时间：
1993-04-01
影响因子：
3.4
通讯作者：
WENNBERG, M
中科院分区：
文献类型：
--
作者：
SEIDEMAN, P;BECK, O;WENNBERG, M
研究了9例类风湿关节炎（RA）患者MTX及其7-羟基代谢物（7-OHMTX）的药代动力学。在随机交叉设计中，每位患者在禁食一晚后接受15毫克MTX静脉注射，静脉注射和口服。测定7 d内MTX和7- ohmtx的血药浓度及24 h内尿量2静脉给药后血浆MTX浓度呈三指数函数，口服给药后呈三指数函数，口服给药后呈三指数函数，注射后呈双指数函数，口服给药后呈零或一阶吸收。在所有三种给药途径后，7-OHMTX的血浆浓度用双指数函数描述。MTX和7-OHMTX的中位末端消除半衰期分别为55 h和116 h。MTX的血药浓度-时间曲线下面积（AUC (0,170 h)）在静脉给药和口服给药之间没有差异，表明这些给药途径后的生物利用度相似。7-OHMTX经静脉、口服和静脉给药后的AUC （0,170 h）值相似。超过80%的MTX以完整药物形式从尿中排出，约3%的MTX在给药后24小时内以7-OHMTX的形式排出在大多数患者中，MTX和7-OHMTX的血浆浓度在给药间隔结束时可测量，这可能有助于识别无反应或副作用风险增加的患者。
1 The pharmacokinetics of MTX and its 7-hydroxy metabolite (7-OHMTX) were investigated in nine patients with rheumatoid arthritis (RA). Each patient received 15 mg MTX i.v., i.m. and p.o. after an overnight fast in a randomized cross-over design. The plasma concentrations of MTX and 7-OHMTX were measured over 7 days and their urinary excretion over 24 h.2 Plasma concentrations of MTX were described by a triexponential function after i.v. administration, a triexponential function with zero or first order absorption after oral administration, and a biexponential function with zero or first order absorption after i.m. injection. Plasma concentrations of 7-OHMTX were described by a biexponential function after all three routes of administration. The median terminal elimination half-lives of MTX and 7-OHMTX were 55 h and 116 h, respectively. The area under the plasma concentration-time curve (AUC (0,170 h)) of MTX did not differ between i.m. and oral administration indicating similar bioavailability after these routes of administration. The AUC (0,170 h) values of 7-OHMTX after i.v., oral and i.m. administration were similar. Over 80% of MTX was excreted in urine as intact drug and about 3% was excreted as 7-OHMTX during 24 h after drug administration.3 Plasma concentrations of MTX and 7-OHMTX were measurable at the end of the dose interval in most of the patients and may help to identify non-responders or patients with increased risk of side-effects.