Dosing Time–Dependency of the Arthritis-Inhibiting Effect of Tacrolimus in Mice

Journal of Pharmacological Sciences

Hiromichi Yoshimatsu¹  Ichiro Ieiri¹  Hideto To²  Ryuji Fukuyama¹  Shun Higuchi¹  Kayo Obayashi¹  Mari Tomonari² 

[1] Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Japan;Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Japan

关键词: tacrolimus;    chronopharmacology;    rheumatoid arthritis;    circadian rhythm;    cytokine;   

DOI  :  10.1254/jphs.11029FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(46)Cited-By(4)Stiffness and cytokine in blood levels show 24-h rhythms in rheumatoid arthritis (RA) patients. We previously revealed that higher therapeutic effects were obtained in RA patients and RA model animals when the dosing time of methotrexate was chosen according to the 24-h rhythms to cytokine. In this study, we examined whether a dosing time–dependency of the therapeutic effect of tacrolimus (TAC) could be detected in collagen-induced arthritis (CIA) and MRL/lpr mice. To measure the levels of cytokines and serum amyloid A (SAA), blood was collected from CIA mice at different times. TAC was administered at two different dosing times based on these findings and its effects on arthritis and toxicity were examined. Plasma tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and SAA concentrations showed obvious 24-h rhythms with higher levels during the light phase and lower levels during the dark phase after RA crisis. The arthritis score and leukocyte counts were significantly lower in the group treated at 2 h after the light was turned on (HALO) than in the control and 14 HALO–treated groups. Our findings suggest that choosing an optimal dosing time could lead to the effective treatment of RA by TAC.

【 授权许可】

Unknown