scholarly journals Validation of limited sampling strategy for the estimation of mycophenolic acid exposure in Chinese adult liver transplant recipients

2007 ◽  
Vol 13 (12) ◽  
pp. 1684-1693 ◽  
Author(s):  
Chen Hao ◽  
Chen Erzheng ◽  
Mao Anwei ◽  
Yu Zhicheng ◽  
Shen Baiyong ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Mycophenolic Acid ◽  
Sampling Strategy ◽  
Acid Exposure ◽  
Limited Sampling Strategy ◽  
Transplant Recipients ◽  
Adult Liver ◽  
Chinese Adult ◽  
Limited Sampling ◽  
Liver Transplant Recipients

Variability in Free Mycophenolic Acid Exposure in Adult Liver Transplant Recipients During the Early Posttransplantation Period

2010 ◽  
Vol 50 (10) ◽  
pp. 1202-1210 ◽  
Author(s):  
Anne Sophie Benichou ◽  
Benoit Blanchet ◽  
Filomena Conti ◽  
Maryline Hornecker ◽  
Denis Bernard ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Mycophenolic Acid ◽  
Acid Exposure ◽  
Transplant Recipients ◽  
Adult Liver ◽  
Liver Transplant Recipients

scholarly journals Limited Sampling Strategy for Estimation of Mycophenolic Acid Exposure in Adult Chinese Heart Transplant Recipients

2021 ◽  
Vol 12 ◽  
Author(s):  
Hongping Xiang ◽  
Hong Zhou ◽  
Jing Zhang ◽  
Yongfeng Sun ◽  
Yirong Wang ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Mycophenolic Acid ◽  
Prediction Error ◽  
Sampling Strategy ◽  
Limited Sampling Strategy ◽  
Transplant Recipients ◽  
Adult Heart ◽  
Chinese Adult ◽  
Limited Sampling ◽  
Heart Transplant Recipients

Background: With the increasing use of mycophenolic acid (MPA) formulations in organ transplantation, the need for personalized immunosuppressive therapy has become well recognized based on therapeutic drug monitoring (TDM) for avoidance of drug-related toxicity while maintaining efficacy. Few studies have assessed area under the 12 h concentration-time curve of MPA (MPA-AUC0–12h) in heart transplant recipients who received mycophenolate mofetil (MMF) dispersible tablets (MMFdt). The aim of the study was to investigate the pharmacokinetics (PK) of MMFdt combined with tacrolimus and further to develop a practical method for estimation of MPA-AUC0–12h using a limited sampling strategy (LSS).Methods: A prospective study in a single center was performed in patients who continuously administrated with MMFdt or MMF capsule (MMFc) for at least 7 days after cardiac transplantation from 2018 to 2020. A total of 48 Chinese adult heart transplant recipients were enrolled. Blood samples were collected before and 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after MMF administration. The validated high-performance liquid chromatography combined with tandem mass spectrometry method was used to measure MPA concentrations. Non-compartmental pharmacokinetic (PK) analysis was applied to calculate the data obtained from individual recipients by WinNonlin. LSS models were developed for MPA-AUC0–12h prediction with multivariate stepwise regression analysis.Results: A large inter-individual variability was observed in AUC0–12h, Tmax, Cmax, MRT0–12h, t1/2 and CL/F after multiple dosing of MMFdt. However, no significant differences were observed between main PK parameters of MMFdt and MMFc. The best estimation of MPA-AUC0–12h was achieved with four points: MPA-AUC0–12h = 8.424 + 0.781 × C0.5 + 1.263 × C2 + 1.660 × C4 + 3.022 × C6 (R2 = 0.844). The mean prediction error (MPE) and mean absolute prediction error (MAPE) of MPA-AUC0–12h were 2.09 ± 14.05% and 11.17 ± 8.52%, respectively. Both internal and external validations showed good applicability for four-point LSS equation.Conclusion: The results provide strong evidence for the use of LSS model other than a single time-point concentration of MPA when performing TDM. A four-point LSS equation using the concentrations at 0.5, 2, 4, 6 h is recommended to estimate MPA-AUC0–12h during early period after transplantation in Chinese adult heart transplant recipients receiving MMFdt or MMFc. However, proper internal and external validations with more patients should be conducted in the future.

Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients

2019 ◽  
Vol 54 (7) ◽  
pp. 652-661 ◽  
Author(s):  
Jia Shao ◽  
Chenyu Wang ◽  
Peng Fu ◽  
Fan Chen ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Transplant ◽  
Distribution Volume ◽  
Therapeutic Window ◽  
Population Pharmacokinetic ◽  
Transplant Recipients ◽  
Adult Liver ◽  
Chinese Adult ◽  
Starting Dose ◽  
Liver Transplant Recipients

Background: Tacrolimus (TAC) is widely used after liver transplantation, but the therapeutic window is narrow. Objective: The purpose was to study both donor and recipient CYP3A5*3 genotypes affecting TAC apparent clearance rate (CL/F) and investigate a TAC population pharmacokinetic (PPK) model in Chinese liver transplant recipients for potential starting-dose individualized medication. Methods: A data set of 721 TAC concentrations was obtained from 43 adult liver transplant recipients. The TAC PPK model was analyzed using nonlinear mixed-effects modeling. Potential covariates, including demographic characteristics, physiological and pathological data, concomitant medications, and CYP3A5*3 genotype, were evaluated. The final model was validated using normalized prediction distribution errors and bootstrapping. Results: A 2-compartment model with first-order absorption and elimination was used to describe TAC disposition. Population estimates of TAC, CL/F, apparent central distribution volume (V2/F), rate of absorption (Ka), and apparent peripheral distribution volume (V3/F) were 18.1 L/h (12%), 72.7 L (34%), 0.163 h−1 (17%), and 412 L (21%), respectively. The model and estimated parameters were found to be stable. Other covariates did not influence TAC CL/F. Both donor and recipient CYP3A5*1 genotypes were significantly correlated with TAC clearance, and CL/F was 1.70-fold higher in both donor and recipient CYP3A5*1 carriers than in noncarriers among Chinese liver transplant recipients. Conclusion and Relevance: A PPK model of TAC was established in Chinese adult liver transplantation recipients for starting-dose individualized medication, which can be expanded to optimize clinical efficacy and minimize toxicity with therapeutic drug monitoring.

Generation and Validation of a Limited Sampling Strategy to Monitor Mycophenolic Acid Exposure in Children With Nephrotic Syndrome

2019 ◽  
Vol 41 (6) ◽  
pp. 696-702 ◽  
Author(s):  
Marcus R. Benz ◽  
Rasmus Ehren ◽  
Daniela Kleinert ◽  
Carsten Müller ◽  
Jutta Gellermann ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Mycophenolic Acid ◽  
Sampling Strategy ◽  
Acid Exposure ◽  
Limited Sampling Strategy ◽  
Limited Sampling
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