Effect of Early Immunosuppression Therapy on De Novo Anti–Human-Leukocyte-Antigen Antibody After Kidney Transplantation

Zhang, H.; Fu, Qian; Zheng, Yifan; Li, J.; Wang, S.; Deng, Ronghai; Huang, Gang; Deng, Wen-feng; Huang, Huiting; Liu, L.; Wang, C.

doi:10.1016/j.transproceed.2018.03.043

Cited by 1 publication

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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