Effects of red blood cell concentrate transfusion on blood tacrolimus concentration

Uchida, Masashi; Yamazaki, Shingo; Suzuki, Takaaki; Takatsuka, Hirokazu; Ishii, Itsuko

doi:10.1007/s11096-020-01038-9

Cited by 6 publications

(3 citation statements)

References 25 publications

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“…The observed inverse correlations between serum albumin levels and TAC concentrations, both in WB and PBMC, could be explained by a higher metabolic activity of the liver, which can be associated with increased drug metabolism. On the other hand, the inverse correlation with hematocrit could be explained by the fact that lower TAC dosages could have been selected in patients with higher hematocrit, since TAC adhesion to erythrocytes can reduce its elimination in the initial phases of therapy (Limsrichamrern et al, 2016;Uchida et al, 2020). In this case, TDM-guided posological adjustments during the first year of therapy would be responsible of these differences, in accordance with the observed negative correlation between the weight-adjusted TAC dose and both albuminemia and hematocrit.…”

Section: Discussionmentioning

confidence: 62%

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

et al. 2021

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Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.

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Section: Discussionmentioning

confidence: 62%

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

et al. 2021

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“…Therefore, we speculated that the onset of GVHD had a limited impact on TCR C/D. In addition, TCR C/D reportedly increased after red blood cell transfusion along with the increase in the hematocrit levels before and after transfusion [ 23 ]. In this study, although 9 of 10 patients received red blood cell transfusions during the observation period, no significant change in hematocrit levels was observed before and after therapeutic IV-MTX administration.…”

Section: Discussionmentioning

confidence: 99%

Elevation of tacrolimus concentration after administration of methotrexate for treatment of graft-versus-host disease in pediatric patients received allogeneic hematopoietic stem cell transplantation

Inoue,

Yamamoto,

Miyata

et al. 2023

J Pharm Health Care Sci

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Background Methotrexate (MTX) is used to treat graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, a case was encountered in which the blood concentration of tacrolimus (TCR) at steady state increased after intravenous MTX administration for GVHD treatment (therapeutic IV-MTX administration). Therefore, this study aimed to investigate the effect of therapeutic IV-MTX administration on the pharmacokinetics of TCR. Methods This single-center, retrospective, observational study included patients who underwent allo-HSCT and received therapeutic IV-MTX administration during immunosuppressive therapy with continuous intravenous infusion (CIV) of TCR from April 2004 to December 2021. Here, each therapeutic IV-MTX administration was defined as a case and independently subjected to subsequent analyses. The blood concentration of TCR at steady state (Css), ratio of Css to daily TCR dose (C/D), and clinical laboratory data were compared before and after therapeutic IV-MTX administration. In addition, dose changes in the TCR after therapeutic IV-MTX administration were evaluated. Results Ten patients (23 cases) were included in this study. The C/D value significantly increased after therapeutic IV-MTX administration (median: 697 vs. 771 (ng/mL)/(mg/kg), 1.16-fold increase, P < 0.05), indicating a reduction in the apparent clearance of TCR. Along with the increase in C/D, significant increases were observed in aspartate transaminase level (median: 51.0 vs. 92.9 U/L, P < 0.01) and alanine aminotransferase level (median: 74.5 vs. 99.4 U/L, P < 0.01) indicating that liver injury after therapeutic IV-MTX administration contributes to the observed C/D increase. In addition, the daily dose of TCR was reduced in 11 cases (47.8%) after therapeutic IV-MTX administration, and the relative frequency of dose reduction tended to be higher than that of dose increase (median: 37.5% vs. 0.0%, P = 0.0519, permuted Brunner-Munzel test). The magnitude of dose reduction was 18.8% (7.4–50.0%) in the 11 cases with dose reduction. Conclusions Therapeutic IV-MTX administration cause a significant increase in C/D, which requires TCR dose reduction. Careful therapeutic drug monitoring of TCR is needed after therapeutic IV-MTX administration in patients receiving immunosuppressive therapy with TCR after allo-HSCT.

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“…In our previous study, there was a correlation between the change in the C/D ratio of tacrolimus (termed “TCR ratio”) and age or body surface area (BSA) [ 29 ]. We also found a correlation between the HCT ratio and age or BSA.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate

Uchida

Hanada

Yamazaki

et al. 2022

J Pharm Health Care Sci

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Background The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC. Methods We enrolled 105 patients (age, 5–66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively). Results The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23, P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate. Conclusions A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.

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Effects of red blood cell concentrate transfusion on blood tacrolimus concentration

Cited by 6 publications

References 25 publications

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

Elevation of tacrolimus concentration after administration of methotrexate for treatment of graft-versus-host disease in pediatric patients received allogeneic hematopoietic stem cell transplantation

Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate

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