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Optimisation de l'administration des médicaments chez les enfants transplantés grâce à la pharmacocinétique de population
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kassir, Nastya |
| Copyright Year | 2013 |
| Abstract | This thesis deals with the application of population pharmacokinetics in order to optimize the use of certain medications in immunocompromised children undergoing transplantation. Among the various drugs used in immunocompromised children, the use of busulfan, tacrolimus and voriconazole remains problematic, particularly because of high interindividual variability in their pharmacokinetics necessitating individualized doses based on therapeutic drug monitoring. In addition, these drugs have not been studied in children and the doses are adapted from adults. This practice does not take into account the pharmacological characteristics of pediatrics throughout their development and makes illusory the extrapolation of data acquired in adults to children. The work done in this thesis studied sequentially the pharmacokinetics of busulfan, voriconazole and tacrolimus by a population approach (non-linear mixed effects models). The developed models have identified the main sources of interindividual variability in the pharmacokinetic parameters of these drugs. The identified covariates are body surface area and weight. These results confirm the importance of taking into account the effect of growth in children. These parameters were allometrically included in the models. This approach allows separating the effect of size from other covariates and enables the comparison of pediatric pharmacokinetic parameters with those of adults. The inclusion of these explanatory covariates should improve the management a priori of patients. The developed models were evaluated to confirm their stability, performance, and their ability to answer the original objectives of modeling. In the case of busulfan, the validated model was used to simulate dosing regimens that improve reaching the target exposure, reduce treatment failure and toxicity episodes. The developed population pharmacokinetic model for voriconazole confirmed the large variability in its pharmacokinetics in immunocompromised children. The limited data did not allow identification of covariates explaining this variability. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/10309/Kassir_Nastya_2012_these.pdf?isAllowed=y&sequence=2 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
