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From pediatric covariate model to semiphysiological function for maturation: part I-extrapolation of a covariate model from morphine to Zidovudine
- Source :
- CPT: Pharmacometrics & Systems Pharmacology, 2012(1), e9, CPT: Pharmacometrics & Systems Pharmacology
- Publication Year :
- 2012
-
Abstract
- New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness-of-fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system-specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP-glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models.CPT: PharmacometricsSystems Pharmacology (2012) 1, e9; doi:10.1038/psp.2012.11; advance online publication 3 October 2012.
- Subjects :
- education.field_of_study
business.industry
Population
Extrapolation
Function (mathematics)
Pharmacology
Bioinformatics
030226 pharmacology & pharmacy
3. Good health
03 medical and health sciences
Zidovudine
0302 clinical medicine
030220 oncology & carcinogenesis
Modeling and Simulation
Covariate
Morphine
Medicine
Pharmacology (medical)
Original Article
Dosing
business
education
Pediatric population
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- CPT: Pharmacometrics & Systems Pharmacology, 2012(1), e9, CPT: Pharmacometrics & Systems Pharmacology
- Accession number :
- edsair.doi.dedup.....634bd0092f8eaa4ae157a4aacd86bf46