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  • External evaluation population pharmacokinetic models in patients with Crohn's disease = Eksterno vrednotenje populacijskih farmakokinetičnih modelov za ustekinumab pri bolnikih s Crohnovo boleznijo : Uniform Master's Study Programme Pharmacy
    Krapež, Vesna, farmacevtka
    Objectives: Crohn’s disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract and reflect in several severe side effects. Current therapeutic guidelines ... recommend a treatment with ustekinumab for moderate-to-severe Crohn’s disease when conventional therapy is ineffective. We will apply population pharmacokinetic modelling for the examination of the ustekinumab pharmacokinetics. Two previously created models will be validated with an external population of patients to evaluate the adequacy of the models for use in other populations for scientific and clinical purposes. The study may lead to an increased understanding of the pharmacokinetics of ustekinumab and other monoclonal antibodies, and optimisation of the treatment of Crohn’s disease. Materials and methods: The study is an evaluation of two prospective observational clinical studies of ustekinumab for populations of Crohn’s disease patients. One study was performed by the Faculty of Pharmacy, University of Ljubljana, and the other was performed by Faculty of Pharmaceutical Sciences, KU Leuven. The data were analysed by cross-validation and data-pooling. Model fits were compared and evaluated with visual predictive check and goodness-of-fit plots, constructed by a computer program NONMEM 7.4.3. Results: The half-life of ustekinumab was in all cases around 17 days, which is approximately consistent with the half-life in other studies (19-22 days). The volumes of distribution were between 5.80 L and 6.87 L. The model by Aguiar Zdovc et al predicted higher distribution of ustekinumab in the peripheral compartment. The volume of distribution in the peripheral compartment was from 3.30 L to 3.36 L for the models by Wang et al and from 0.75 L to 2.63 L for the models by Aguiar Zdovc et al. The values of clearance were similar and took values between 0.235 L/day and 0.291 L/day. The predictive performance of the model by Aguiar Zdovc et al on pooled dataset was better than that of the model by Wang et al. Conclusion: The models of a study adequately estimated the patients’ parameters, although the fit was not always optimal. The model by Wang et al was more flexible for adaptations to the Ljubljana and pooled dataset, although the model by Aguiar Zdovc et al included more critical parameters that needed to be considered, particularly those related to target mediated kinetics. We can conclude that we successfully evaluated the population pharmacokinetic models for ustekinumab in patients with Crohn’s disease.
    Vrsta gradiva - magistrsko delo ; neleposlovje za odrasle
    Založništvo in izdelava - Ljubljana : [V. Krapež], 2022
    Jezik - angleški
    COBISS.SI-ID - 124703747

Knjižnica/institucija Kraj Akronim Za izposojo Druga zaloga
Fakulteta za farmacijo, Ljubljana Ljubljana FFALJ v čitalnico 1 izv.
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