Angelis-Stoforidis P, Vajda F J, Christophidis N
Department of Clinical Pharmacology, St. Vincent's Hospital, Victoria, Australia.
Clin Exp Rheumatol. 1999 May-Jun;17(3):313-20.
To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects.
Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay.
E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15).
The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.
测定类风湿关节炎（RA）患者循环红细胞（E-MTX）、单核细胞（MNC-MTX）和多形核白细胞（PMN-MTX）中的甲氨蝶呤多聚谷氨酸盐，并观察其是否与临床疗效及副作用相关。
65例（40例女性，25例男性；平均年龄57岁）符合RA（ARA修订标准）且接受每周脉冲式甲氨蝶呤（2.5 - 37.5 mg）治疗至少2个月的患者纳入本研究。在采集血液进行甲氨蝶呤测定时，将患者分为反应者（R）、部分反应者（PR）或无反应者（NR）。记录自开始使用甲氨蝶呤以来的副作用。采用酶法测定甲氨蝶呤多聚谷氨酸盐（对临床细节设盲）。
反应者和部分反应者的E-MTX显著高于无反应者（p < 0.001）。同样，PMN-MTX也较高，但仅R组差异有统计学意义（p = 0.0019）。浓度差异不能用剂量来解释，NR组的剂量往往高于R组（p = 0.085）。R组的泼尼松龙伴随剂量显著低于NR组（p = 0.001），血沉和C反应蛋白也是如此（分别为p = 0.007和p = 当血液被采集用于MTX测定时，患者被分类为反应者（R）、部分反应者（PR）或无反应者（NR）。自MTX开始使用以来的副作用也被记录下来。使用酶法测定MTX - 多聚谷氨酸盐（对临床细节不知情）。
反应者和部分反应者的E - MTX显著高于无反应者（p < 0.001）。同样，PMN - MTX也更高，但差异仅在R组有统计学意义（p = 0.0019）。浓度差异不能基于剂量来解释，NR组的剂量往往高于R组（p = 0.085）。R组的泼尼松龙伴随剂量显著低于NR组（p = 0.001），血沉和C反应蛋白也是如此（分别为p = 0.007和p = 0.05），但平均红细胞体积更高（p = 0.047）。有副作用的患者E - MTX往往更高，但这种差异未达到统计学意义（p = 0.15）。
结果表明，RA患者红细胞和多形核白细胞中MTX多聚谷氨酸盐的循环细胞内水平与临床疗效相关，但与毒性无关。 05），但平均红细胞体积更高（p = 0.047）。有副作用的患者E - MTX往往更高，但这种差异未达到统计学意义（p = 0.15）。
结果表明，RA患者红细胞和多形核白细胞中MTX多聚谷氨酸盐的循环细胞内水平与临床疗效相关，但与毒性无关。
