Chronopharmacokinetic Study of a New Immunosuppressive Agent, FK 506, in Mice

Fujimura, Akio; Shiga, Tsuyoshi; Ohashi, K.; Ebihara, Akio

doi:10.1254/jjp.61.137

Cited by 15 publications

(4 citation statements)

References 4 publications

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“…In past reports, no difference in dosing timedependent pharmacokinetics was found, which agrees with the present study (38). On the other hand, many reports have demonstrated that the blood concentration of TAC shows daily variations in which its C max is markedly increased in the active phase compared with the inactive phase (27,39,40). The main difference between these reports and our study was the route of administration.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2011

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Abstract. 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.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2011

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“…However, it is unclear whether similar AUC between daytime and night- time brings the best clinical outcome since animal experiments have demonstrated that tacrolimus toxicity depends on the dosing time. [27][28][29] MMF was coadministered with tacrolimus twice a day in all patients from 2 days before renal transplantation, but this did not significantly alter tacrolimus pharmacokinetics. 30,31 Gastrointestinal events such as diarrhea raise the tacrolimus concentration, 32 and while the use of MMF often results in diarrhea, there were no such events during the blood-sampling period of this study.…”

Section: Discussionmentioning

confidence: 99%

Chronopharmacokinetics of Tacrolimus in Kidney Transplant Recipients: Occurrence of Acute Rejection

Tada

Satoh

Iinuma

et al. 2003

The Journal of Clinical Pharma

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The circadian variation of clinical pharmacokinetics of tacrolimus was studied using 16 adult renal transplant recipients 1 month after the operation. The recipients were administered tacrolimus twice a day (9 a.m. and 9 p.m.), and whole-blood samples were obtained just prior to and 1, 2, 3, 6, 9, and 12 hours after oral administration. Histological specimens of transplant kidney were collected by an allograft core biopsy on day 28 after the transplantation. There were no circadian changes in the area under the concentration-time curve (AUC0-12) (214 ng.h/mL during daytime vs. 223 ng.h/mL during nighttime) resulting from morning and night doses. A slight delay in mean residence time (MRT0-12) and time to the peak concentration (tmax) was found after night doses, but there was no statistical significance. Three patients (18.8%) had a clinical acute rejection (AR) episode 4 to 6 weeks after transplantation, and AUC0-12 at nighttime was significantly lower (18.4% on average) in patients with AR in comparison to those without AR. There was no statistical significance in maximum concentration (Cmax) or morning/night trough levels between patients with and without AR. In regard to the correlation between tacrolimus concentrations in each sampling time and AUC0-12, the morning trough concentrations were less predictable for daytime AUC0-12 (r2 = 0.125), but there was a weak correlation to nighttime AUC0-12 (r2 = 0.424). Tacrolimus concentrations at 2, 3, and 6 hours after the morning dose (C2, C3, and C6) had a good correlation against daytime AUC. The results of this study indicate that the variance on the clinical pharmacokinetics of tacrolimus between daytime and nighttime in renal transplant patients is not significant, while the lower nighttime AUC corresponded to the occurrence of AR.

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“…In Group 1 total ACR were 12 (35.3%); in Group 2 total ACR were 27(24.1%); and in Group 3 total ACR were 5(15.2%). This is shown in Table 15 [101][102][103][104][105]. Banff grading of these rejection episodes showed that grade 2 and grade 3 rejection were absent in Group 3, as seen clearly in Table 16 [105][106][107][108][109][110].…”

Section: Rejectionsmentioning

confidence: 90%

Correlation of Tough Tacrolimus Level with Early Acute Rejections in Renal Allograft Recipients - A Prospective Study

Tripathi¹

2018

JOJUN

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Many transplantation centers advocate the administration of immunosuppression pre-transplant, with a variation of one to five pre-operative days, while other centers only start the therapy after the surgery. The potential disadvantages of early administration of immunosuppression therapy are the risk of infection and the nephrotoxicity effects of calcineurin inhibitors during allograft reperfusion [11][12][13][14][15][16][17][18][19][20].Up to the present moment, there is only one systematic study that addresses the impact of pre-transplant administration of immunosuppressive therapy consisting of cyclosporine as the CNI, on incidence and severity of acute rejection. Materials and Methods Study designThis is an open label randomized study consisting of renal allograft recipients from living donors. This study was carried out by Department of Nephrology, at a tertiary level referral hospital in western India, between January 2008 to September 2009. All patients enrolled were older than 18 years. The

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Chronopharmacokinetic Study of a New Immunosuppressive Agent, FK 506, in Mice

Cited by 15 publications

References 4 publications

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

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

Chronopharmacokinetics of Tacrolimus in Kidney Transplant Recipients: Occurrence of Acute Rejection

Correlation of Tough Tacrolimus Level with Early Acute Rejections in Renal Allograft Recipients - A Prospective Study

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