Systemic exposure to 5‐fluorouracil and its metabolite, 5,6‐dihydrofluorouracil, and development of a limited sampling strategy for therapeutic drug management of 5‐fluorouracil in patients with gastrointestinal malignancy

Therapeutic drug monitoring of ibrutinib is based on the area under the curve of concentration vs. time (AUCIBRU) instead of trough concentration (Cmin,ss) because of a limited accumulation in plasma. Our objective was to identify a limited sampling strategy (LSS) to estimate AUCIBRU associated with Bayesian estimation. The actual AUCIBRU of 85 patients was determined by the Bayesian analysis of the full pharmacokinetic profile of ibrutinib concentrations (pre-dose T0 and 0.5, 1, 2, 4 and 6 h post-dose) and experimental AUCIBRU were derived considering combinations of one to four sampling times. The T0–1–2–4 design was the most accurate LSS (root-mean-square error RMSE = 11.0%), and three-point strategies removing the 1 h or 2 h points (RMSE = 22.7% and 14.5%, respectively) also showed good accuracy. The correlation between the actual AUCIBRU and Cmin,ss was poor (r2 = 0.25). The joint analysis of dihydrodiol-ibrutinib metabolite concentrations did not improve the predictive performance of AUCIBRU. These results were confirmed in a prospective validation cohort (n = 27 patients). At least three samples, within the pre-dose and 4 h post-dose period, are necessary to estimate ibrutinib exposure accurately.

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LIMITED SAMPLING STRATEGY TO ESTIMATE SYSTEMIC EXPOSURE TO THE IMMUNOSUPPRESSIVE DRUG MYCOPHENOLIC ACID IN HEART TRANSPLANTATION (HTx).

Transplantation Journal ◽

10.1097/00007890-200607152-01455 ◽

2006 ◽

Vol 82 (Suppl 2) ◽

pp. 556

Author(s):

&NA;

Keyword(s):

Heart Transplantation ◽

Mycophenolic Acid ◽

Systemic Exposure ◽

Sampling Strategy ◽

Immunosuppressive Drug ◽

Limited Sampling Strategy ◽

Limited Sampling

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Therapeutic Drug Monitoring of Micophenolate Mofetil in Cardiac Transplant Patients by Limited Sampling Strategy: An Update

Topics in Heart Failure Management ◽

10.5772/intechopen.80027 ◽

2019 ◽

Author(s):

Massimo Baraldo ◽

Sandro Sponga ◽

Ugolino Livi

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Sampling Strategy ◽

Limited Sampling Strategy ◽

Therapeutic Drug ◽

Cardiac Transplant ◽

Transplant Patients ◽

Limited Sampling

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

Current Clinical Pharmacology ◽

10.2174/1574884715666200827104813 ◽

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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