Limited Sampling Strategy for the Estimation of Tacrolimus Area Under the Concentration-Time Curve in Chinese Adult Liver Transplant Patients

Pharmacology ◽  
2016 ◽  
Vol 98 (5-6) ◽  
pp. 229-241 ◽  
Author(s):  
Xiao-Xue Liu ◽  
Bei-Ming Xu ◽  
Hao Chen ◽  
Yan-yan Song ◽  
Wan-hua Yang ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Sampling Strategy ◽  
Limited Sampling Strategy ◽  
Adult Liver ◽  
Time Curve ◽  
Transplant Patients ◽  
Chinese Adult ◽  
Limited Sampling ◽  
Concentration Time

scholarly journals Limited Sampling Strategy for the Estimation of Mycophenolic Acid and its Acyl Glucuronide Metabolite Area under the Concentration-Time Curve in Japanese Lung Transplant Recipients

2019 ◽  
Vol 22 ◽  
pp. 407-417 ◽  
Author(s):  
Masaki Tanaka ◽  
Masafumi Kikuchi ◽  
Shinya Takasaki ◽  
Tensei Hirasawa ◽  
Kensuke Sigeta ◽  
...  
Keyword(s):  
Mycophenolic Acid ◽  
Lung Transplant ◽  
Sampling Strategy ◽  
Prediction Errors ◽  
Time Curve ◽  
Transplant Patients ◽  
Acyl Glucuronide ◽  
Limited Sampling ◽  
Concentration Time ◽  
Time Point

Purpose: The dose of mycophenolate mofetil (MMF) used to prevent rejection after lung transplantation is often adjusted based on the 12-hour area under the concentration-time curve (AUC0-12) of mycophenolic acid (MPA). A limited sampling strategy (LSS) is useful to define the pharmacokinetic (PK) profiles of MPA and mycophenolic acid acyl glucuronide (AcMPAG). Therefore, this study aimed to design a LSS based on multiple linear regression for estimating the AUC0-12 of MPA and AcMPAG at the minimum blood sampling points in Japanese lung transplant patients with concomitant tacrolimus. Methods: Forty-five lung transplantation recipients were enrolled in a PK study of MPA, mycophenolic acid glucuronide (MPAG), and AcMPAG. The plasma MPA, MPAG, and AcMPAG concentrations were determined just before and at 0.5, 1, 2, 4, 8, and 12 hours after dosing. The AUC0-12 of MPA and AcMPAG was calculated using a linear trapezoidal rule from the plasma concentration of each blood sampling time. LSS was used to develop models for estimated AUC in the model group (n = 23) and was evaluated in the validation group (n = 22). Results: The best three time-point equation was 4.04 + 1.64·C1 + 3.08·C4 + 5.17·C8 for MPA, and -0.13 + 3.01·C1 + 3.51·C4 + 5.74·C8 for AcMPAG. The prediction errors (PE) and the absolute prediction errors (APE) were within the clinically acceptable ± 5% and 15% range, respectively (MPA: PE = 2.00%, APE = 11.66%, AcMPAG: PE = 0.98%, APE = 14.69%). The percentage of estimated AUC0-12 within ± 15% of the observed AUC0-12 was 77.27% for MPA and 81.82% for AcMPAG. Conclusion: LSS using three time-point (C1, C4, and C8) provides the most reliable and accurate simultaneous estimation of the AUC0-12 of MPA and AcMPAG in Japanese lung transplant patients.

Estimation of Abbreviated Mycophenolic Acid Area Under the Concentration-Time Curve during Stable Post-transplant Period by Limited Sampling Strategy

2020 ◽  
Vol 15 ◽  
Author(s):  
Asieh Karimani ◽  
Hasan Abedi ◽  
Fatemeh Nazemian ◽  
Atena Poortaji ◽  
Amir Hooshang Mohammad pour
Keyword(s):  
Renal Transplantation ◽  
Prediction Error ◽  
Sampling Strategy ◽  
Limited Sampling Strategy ◽  
Stable Phase ◽  
Therapeutic Drug ◽  
Time Curve ◽  
Limited Sampling ◽  
Concentration Time ◽  
Over Time

Background: The area under the concentration-time curve (AUC) of mycophenolic acid (MPA), is a valid prognosticator of the risk of rejection and the gold standard in its therapeutic drug monitoring (TDM), over time posttransplantation. Objective: This study aimed to investigate MPA pharmacokinetic parameters, as well as developing a limited sampling strategy (LSS) to estimate an abbreviated MPA AUC, in the stable phase post-renal transplantation. Methods: In this study 19 patients with normal graft function (glomerular filtration rate >70 ml/min) who fulfilled inclusion & exclusion criteria were involved. Blood samples at various times were taken in the stable phase after transplantation. MPA plasma concentration was measured by reverse-phase high-performance liquid chromatography. MPA AUC0–12h was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal time points of MPA levels that could be used to yield model equations best fitted to MPA AUC 0- 12h. The findings of this study were compared with the results of our previous study, which was done similarly in the early phase post-renal transplantation. Results: The results demonstrated that the MPA-AUC and clearance were not affected over time, but MPA-tmax was significantly lower in the stable phase in comparison with the early phase (P=0.001). The best regression equation for AUC estimation in the stable phase was AUC=9.57*C6+27.238 (r2=0.907). The validation of the method was performed using the jackknife method. The mean prediction error of these models was not different from zero (P > 0.05) and had a high root mean square prediction error (7.91). Conclusion: In conclusion, the pharmacokinetics of MPA could be affected by time after transplantation, make it essential to develop a limited sampling strategy granted an efficacious approach for therapeutic drug monitoring during the stable post-transplant period.

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