The efficacy and safety of intensified enteric-coated mycophenolate sodium with low exposure of calcineurin inhibitors in Chinese<i>de novo</i>kidney transplant recipients: a prospective study

Zhang, H.; Liu, L.; Li, J.; Fu, Qian; Wan, Jianxin; Deng, Ronghai; Wang, H.; Liu, Jun; Deng, Wen-feng; Deng, Shijie; Chen, L.; Wang, C.

doi:10.1111/ijcp.12813

Cited by 6 publications

(2 citation statements)

References 20 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are consistent with the studies that suggest an inverse association between MPA exposure and a risk of AR. [ 9 10 ] Adequate MPA exposure in the early posttransplant phases is required because patients are at the highest risk of AR during this period. A therapeutic window of MPA-AUC has been recommended (30–60 mg·h -1 ·L -1 ) to achieve optimal efficacy.…”

Section: Discussionmentioning

confidence: 99%

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

Ding

Lizi

Han³

et al. 2018

Chinese Medical Journal

View full text Add to dashboard Cite

Background:Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.Methods:We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC)0-12h and Tac C0 were measured at the 1st week and the 1st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.Results:The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC0-12h at the 1st week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUC0-12h level was <30 mg·h-1·L-1 at the 1st week (15.0% vs. 44.4%) or the Tac C0 was <4 ng/ml at the 1st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC0-12h at the 1st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C0 at the 1st month (OR: 0.904, 95% CI: 0.822–0.986) had significant inverse correlation with BPAR (P < 0.05).Conclusions:Low-level exposure of MPA and Tac C0 in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC0-12h <30 mg·h-1·L-1 and Tac C0 <4 ng/ml should be avoided in the first few weeks after transplantation.

show abstract

Section: Discussionmentioning

confidence: 99%

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

Ding

Lizi

Han³

et al. 2018

Chinese Medical Journal

View full text Add to dashboard Cite

show abstract

“…MMF) and interleukin receptor blockers (e.g. basiliximab) is advocated to diminish the risk of rejection [11,[51][52][53][54]. In heart transplants, initiation of tacrolimus may even be postponed for 1 week when an Time (hr) Conditional weighted residuals Fig.…”

Section: Future Perspectivesmentioning

confidence: 99%

High Variability of Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation

Sikma

Hunault

Maarseveen

et al. 2019

Eur J Drug Metab Pharmacokinet

View full text Add to dashboard Cite

Background and Objective Oral tacrolimus is initiated perioperatively in heart and lung transplantation patients. There have been few studies on oral tacrolimus pharmacokinetics early post-transplantation, even though tacrolimus-related toxicity may occur early, potentially leading to morbidity and mortality. Therefore, we aimed to study the pharmacokinetics of oral tacrolimus in thoracic organ recipients during the first days after transplantation. Methods We conducted a pharmacokinetic study in 30 thoracic organ transplants at intensive care at the University Medical Center Utrecht in the first week post-transplantation. Twelve-hour whole-blood tacrolimus profiles were examined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and analysed via population pharmacokinetic modelling. Results The concentration-time profiles showed high variability. Concentrations at 12 h were outside the target range in 69% of the cases. A two-compartment model with mixed first-order and zero-order absorption adequately described tacrolimus concentrations. The typical value of the apparent clearance was 19.6 L/h (95% CI 16.2-22.9), and the apparent distribution volumes of central and peripheral compartments, V1 and V2, were 231 L (95% CI 199-267) and 521 L (95% CI 441-634), respectively. Inter-occasion (dose-to-dose) variability far exceeded the interindividual variability (IIV), with an estimated variability in relative bioavailability of 55% (95% CI 48.5-64.4). Conclusions The high variability of tacrolimus pharmacokinetics early after thoracic organ transplantation is largely due to excessive variability in bioavailability, making individualised dosing based on measured concentrations futile. To bypass this bioavailability issue, we suggest administering tacrolimus intravenously and aiming below the upper therapeutic range early post-transplantation. Clinical Trial Registraion: NTR 3912/EudraCT 2012-001909-24.

show abstract

Adverse effects of mycophenolic acid in renal transplant recipients: gender differences

Spasić

Catić‐Đorđević

Veličković‐Radovanović

et al. 2019

Int J Clin Pharm

View full text Add to dashboard Cite

The efficacy and safety of intensified enteric-coated mycophenolate sodium with low exposure of calcineurin inhibitors in Chinesede novokidney transplant recipients: a prospective study

Abstract: The intensified EC-MPS dosing regimen maintaining low-dose CNIs in this study may be beneficial for Chinese adult de novo kidney transplant recipients in terms of acute rejection and allograft function and is safe within 6 months post transplant.

Cited by 6 publications

References 20 publications

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

High Variability of Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation

Adverse effects of mycophenolic acid in renal transplant recipients: gender differences

Contact Info

Product

Resources

About