A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents
| العنوان: | A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents |
|---|---|
| المؤلفون: | Susan M. Abdel-Rahman, Jonathan B. Wagner, Kayode Ogungbenro, Aleksandra Galetin, J. Steven Leeder |
| المصدر: | European Journal of Clinical Pharmacology Ogungbenro, K, Wagner, J B, Abdel-Rahman, S, Leeder, J S & Galetin, A 2019, ' A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents ', European journal of clinical pharmacology . https://doi.org/10.1007/s00228-019-02697-yTest, https://doi.org/10.1007/s00228-019-02697-yTest |
| بيانات النشر: | Springer Berlin Heidelberg, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Simvastatin, Metabolite, Pharmacology, 030226 pharmacology & pharmacy, chemistry.chemical_compound, 0302 clinical medicine, population pharmacokinetics, polycyclic compounds, Metabolites, Cytochrome P-450 CYP3A, Pharmacology (medical), 030212 general & internal medicine, Population pharmacokinetics, Child, metabolites, education.field_of_study, biology, Liver-Specific Organic Anion Transporter 1, General Medicine, children and adolescents, lipids (amino acids, peptides, and proteins), Female, medicine.drug, Adult, Children and adolescents, Adolescent, Genotype, Population, Hyperlipidemias, Models, Biological, Modelling, modelling, 03 medical and health sciences, Young Adult, Pharmacokinetics, medicine, Humans, cardiovascular diseases, Dosing, education, CYP3A5, Active metabolite, business.industry, organic chemicals, nutritional and metabolic diseases, Pharmacokinetics and Disposition, chemistry, biology.protein, Hydroxymethylglutaryl-CoA Reductase Inhibitors, SLCO1B1, business |
| الوصف: | Purpose Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status. Methods Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg C (rs4149056) on the pharmacokinetics of the active metabolite simvastatin acid in children/adolescents, consistent with adult data. In addition, age was identified as a covariate affecting elimination clearances of 6-hydroxymethyl simvastatin acid and 3, 5 dihydrodiol simvastatin metabolites. Conclusion The model developed describes the pharmacokinetics of simvastatin and its metabolites in children/adolescents capturing the effects of both c.521T>C and age on variability in exposure in this patient population. This joint simvastatin metabolite model is envisaged to facilitate optimisation of simvastatin dosing in children/adolescents. Electronic supplementary material The online version of this article (10.1007/s00228-019-02697-y) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1432-1041 0031-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::699bc3230303aacd3a9c86415f651c74Test http://europepmc.org/articles/PMC6697721Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....699bc3230303aacd3a9c86415f651c74 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321041 00316970 |
|---|