Kremer J M, Hamilton R A
Department of Medicine, Albany Medical College, NY 12208, USA.
J Rheumatol. 1995 Nov;22(11):2072-7.
To determine the pharmacokinetics of methotrexate (MTX) with and without nonsteroidal antiinflammatory drugs (NSAID) at a 7.5 mg dose and higher usual maintenance doses of the drug. To determine the difference in pharmacokinetic variables when salicylate and nonsalicylate NSAID are administered with MTX at these doses.
Thirty patients receiving MTX chronically underwent a study of MTX pharmacokinetics after 7.5 mg doses of MTX with their usual NSAID and after the NSAID were withheld for 5 half-lives. Sixteen additional patients underwent pharmacokinetics studies with and without NSAID while receiving their usual weekly maintenance dose of MTX of 16.6 (3.6) mg (Mean +/- SD).
No significant differences in pharmacokinetic variables were observed with and without NSAID at the 7.5 mg weekly dose of MTX. When patients received usual maintenance doses of MTX the renal clearance of MTX NSAID was 91.7 (26.4) ml/min versus 115.3 (34.4) ml/min without NSAID (p = 0.004). Creatinine clearance in patients taking usual maintenance doses increased from 77.5 (13.9) ml/min with NSAID to 95.3 (26.3) ml/min without NSAID (p = 0.05). A reduction in renal clearance of MTX was observed with maintenance dose MTX in both the 4 patients taking salicylates (p = 0.016) and the 12 patients taking nonsalicylate NSAID (p = 0.024).
NSAID produce significant decreases in renal clearance of MTX and creatinine when patients consume their usual weekly dose of the drug, but not when they take a 7.5 mg dose. This effect is likely to achieve clinical relevance across the dose ranges used to treat patients with rheumatoid arthritis.
确定7.5毫克剂量以及更高常规维持剂量的甲氨蝶呤（MTX）在联用和不联用非甾体抗炎药（NSAID）时的药代动力学。确定在这些剂量下，水杨酸类和非水杨酸类NSAID与MTX联用时药代动力学变量的差异。
30例长期接受MTX治疗的患者在服用7.5毫克剂量MTX及联用常规NSAID后，以及在NSAID停药5个半衰期后，进行了MTX药代动力学研究。另外16例患者在接受16.6（3.6）毫克（均值±标准差）的常规每周维持剂量MTX时，进行了联用和不联用NSAID的药代动力学研究。
在每周7.5毫克剂量的MTX治疗中，联用和不联用NSAID时，药代动力学变量未观察到显著差异。当患者接受MTX常规维持剂量时，联用NSAID时MTX的肾清除率为91.7（26.4）毫升/分钟，不联用NSAID时为115.3（34.4）毫升/分钟（p = 0.004）。服用常规维持剂量的患者，肌酐清除率从联用NSAID时的77.5（13.9）毫升/分钟增加到不联用NSAID时的95.3（26.3）毫升/分钟（p = 0.05）。在4例服用水杨酸类药物的患者（p = 0.016）和12例服用非水杨酸类NSAID的患者（p = 0.024）中，均观察到维持剂量MTX使MTX的肾清除率降低。
当患者服用常规每周剂量的药物时，NSAID会使MTX和肌酐的肾清除率显著降低，但服用7.5毫克剂量时则不会。在用于治疗类风湿关节炎患者的剂量范围内，这种效应可能具有临床相关性。
