scholarly journals P30 Limited sampling strategies to predict valganciclovir exposure in kidney transplanted children

2019 ◽  
Vol 104 (6) ◽  
pp. e29.2-e29
Author(s):  
N Benyoub ◽  
A Facchin ◽  
S Magreault ◽  
E Jacqz-Aigrain ◽  
V Elie
Keyword(s):  
Model Development ◽  
Area Under The Curve ◽  
Sampling Strategy ◽  
Therapeutic Drug ◽  
Pharmacokinetic Data ◽  
Multilinear Regression ◽  
Post Dose ◽  
Blood Samples ◽  
Limited Sampling ◽  
Pharmacokinetic Profiles

BackgroundGanciclovir and its pro-drug, valganciclovir, are anti-viral drugs used in cytomegalovirus infections treatment in kidney transplanted children. Both present a high pharmacokinetic variability requiring dosage individualization and Therapeutic Drug Monitoring to ensure optimal therapeutic exposure. This retrospective monocentric study aimed to develop a Limited Sampling Strategy (LSS) predicting Area Under the Curve (AUC0-24h) reducing the number of blood samples to improve and facilitate kidney transplanted children medical care.MethodsPediatric kidney transplanted children treated with valganciclovir were included. Rich pharmacokinetic data from ganciclovir plasmatic dosages (sampling times at 0h, 1h, 2h, 4h, 8h, 12 h and 24 h) were collected between February 2005 and November 2018. Ganciclovir exposures at steady-state (AUC0-24h) were calculated using the trapezoidal method. The LSS was developed using a multilinear regression approach to predict AUC0-24h. The overall patients population was divided into two groups for model development and validation purposes.Results129 patients were included: 46 girls and 83 boys, mean age at transplantation was 11.3years ± 5.1. Multilinear regression models were developed on 85 pharmacokinetic profiles (85 patients, mean AUC0-24h=64µg.h/mL ± 27, creatinine clearance=72.4 mL/min per 1.73 m2) and validated on an independent group of 73 pharmacokinetic profiles (44 patients). Regressions based on samples collected at 0, 2, 4 h (R=0.946) or 0, 2, 8 h (R=0.968) presented the best AUC0-24h predictive performances (RMSE=7.5 and 6.6, MAE=5.7 and 4.8 respectively) with an average difference between reference and predicted AUC0-24h of -0.52 and 0.67µg.h/mL respectively.ConclusionsTo date, this is the largest cohort of valganciclovir treated pediatric transplanted children used to develop a LSS. This LSS allows to accurately predict ganciclovir AUC0-24h in pediatric transplanted patients using 3 pharmacokinetic blood samples at 0h, 2h, and 4 h post-dose. Beside other Bayesian estimators developed in the literature, this multilinear regression can be easily implemented into daily practice facilitating patients care.Disclosure(s)Nothing to disclose

scholarly journals Limited Sampling Strategy for Determination of Ibrutinib Plasma Exposure: Joint Analyses with Metabolite Data

2021 ◽  
Vol 14 (2) ◽  
pp. 162
Author(s):  
Félicien Le Louedec ◽  
Fanny Gallais ◽  
Fabienne Thomas ◽  
Mélanie White-Koning ◽  
Ben Allal ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Sampling Strategy ◽  
Predictive Performance ◽  
Pharmacokinetic Profile ◽  
Limited Sampling Strategy ◽  
Joint Analysis ◽  
Therapeutic Drug ◽  
Post Dose ◽  
Limited Sampling ◽  
Three Samples

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.

Determination of mycophenolate area under the curve by limited sampling strategy

2001 ◽  
Vol 33 (1-2) ◽  
pp. 1052-1053 ◽  
Author(s):  
S Yeung ◽  
K.L Tong ◽  
W.K Tsang ◽  
H.L Tang ◽  
K.S Fung ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Sampling Strategy ◽  
Limited Sampling Strategy ◽  
Limited Sampling

Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU): new preanalytic aspects

2019 ◽  
Vol 57 (7) ◽  
pp. 1012-1016 ◽  
Author(s):  
Sonani Mindt ◽  
Sihem Aida ◽  
Kirsten Merx ◽  
Annette Müller ◽  
Tobias Gutting ◽  
...  
Keyword(s):  
Dose Adjustment ◽  
Area Under The Curve ◽  
Dose Calculation ◽  
Therapeutic Drug ◽  
Individual Dose ◽  
Blood Samples ◽  
Sampling Points ◽  
Port System ◽  
The Right ◽  
Edta Blood

Abstract Background 5-Fluorouracil (5-FU) is frequently used for the treatment of gastrointestinal tumors. The pharmacological effect of 5-FU is influenced by genetic polymorphisms as well as differently dosed regimens. Currently, 5-FU is generally administered as a continuous infusion via an implanted port system using a body surface area (BSA)-based dose calculation. In order to optimize treatment, the area under the curve (AUC) can be estimated to allow for individual dose adjustment. A 5-FU AUC range between 20 and 30 [mg×h×L] is recommended. The aim of the current study was to assess if blood for AUC analysis could also be drawn at the side where the port system had been placed. Methods We collected EDTA blood samples of patients receiving infusional 5-FU simultaneously from different sampling points (right/left cubital vein). 5-FU concentrations were measured in a steady-state equilibrium based on nanoparticle immunoassay (My5-FU; Saladax). Results A total of 39 patients took part in this study. About half of the patients did not reach the target 5-FU concentration window (37% were under- and 16% of the patients were overdosed). Calculated median AUC was 23.3 for the right arm (range 5.8–59.4) and a median of 23.4 for the left arm (range 5.3–61.0). AUC values showed no difference between right compared to left arms (p=0.99). Conclusions In all, these results confirm that a high percentage of patients are not treated with 5-FU doses reaching suggested AUC levels of 20–30. The location of venepuncture, however, had no impact on the results of plasma 5-FU concentration.

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