Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.
J Pharm Pharmacol. 2017 Sep;69(9):1145-1154. doi: 10.1111/jphp.12752. Epub 2017 May 31.
Methotrexate (MTX) is administered once or thrice weekly to patients with rheumatoid arthritis (RA). Even though RA continually progresses, MTX is not administered daily. Therefore, we investigated whether the daily administration of a low dose of MTX inhibits the progression of arthritis in collagen-induced arthritis (CIA) rats.
Methotrexate was orally administered once weekly, thrice weekly and once daily to CIA rats, and arthritis scores were measured.
When the same dose of MTX was administered, the exacerbation of arthritis was inhibited significantly more in the once-daily group than in the other groups. When the dose in the once-daily group was reduced to one-fourth that of the current standard dosing method, arthritis scores were markedly lower in the once-daily group than in the once and thrice-weekly groups.
The daily administration of a low dose of MTX not only maintained normal levels that estimated adverse effects but also suppressed the progression of arthritis significantly more than the current standard dosing method. The results indicate that the reconsideration of dosing schedules based on the characteristics of MTX will lead to more effective RA therapy than that currently used in clinical practice.
甲氨蝶呤(MTX)每周给药 1 次或 3 次,用于治疗类风湿关节炎(RA)患者。尽管 RA 持续进展,但 MTX 并非每日给药。因此,我们研究了每日给予低剂量 MTX 是否会抑制胶原诱导性关节炎(CIA)大鼠关节炎的进展。
将 MTX 每周一次、每周三次和每日一次口服给予 CIA 大鼠,并测量关节炎评分。
当给予相同剂量的 MTX 时,每日给药组的关节炎恶化程度明显低于其他组。当每日给药组的剂量减少至当前标准给药方法的四分之一时,每日给药组的关节炎评分明显低于每周一次和每周三次给药组。
每日给予低剂量 MTX 不仅维持了估计不良反应的正常水平,而且比当前标准给药方法更显著地抑制了关节炎的进展。这些结果表明,基于 MTX 的特性重新考虑给药方案将导致比目前临床实践中使用的更有效的 RA 治疗。