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Effects of the FcRn developmental pharmacology on the pharmacokinetics of therapeutic monoclonal IgG antibody in pediatric subjects using minimal physiologically-based pharmacokinetic modelling
- Source :
- mAbs. :1-13
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab and palivizumab) were used. The adult group contained six subjects with weights from 50 to 100 kg. For pediatric subjects, seven age groups were assumed, with five subjects each having the weight of 95%, 75%, 50%, 25% and 5% percentile of the population. A first evidence-based rating system to evaluate the quality of the source data used to derive pediatric-specific mPBPK model parameter was proposed. A stepwise approach was used to examine the best combination of age/weight effect on the parameters of the mPBPK model in adult and pediatric subjects. IgG synthesis rate (K(syn)), extravasation rate (ER) and FcRn were fitted simultaneously to the PK of bevacizumab and native-IgG in both adult and pediatric. All fitting showed good fits based on the graphs and the coefficient of variation of the fitted parameters (
- Subjects :
- Adult
Physiologically based pharmacokinetic modelling
IgG synthesis rate
Immunology
Receptors, Fc
Pharmacology
Models, Biological
030226 pharmacology & pharmacy
Monoclonal IgG
Young Adult
03 medical and health sciences
0302 clinical medicine
Neonatal Fc receptor
Pharmacokinetics
Report
Humans
Immunology and Allergy
Medicine
Child
Palivizumab
Evidence-Based Medicine
biology
business.industry
Body Weight
Histocompatibility Antigens Class I
Developmental pharmacology
Bevacizumab
Child, Preschool
Immunoglobulin G
030220 oncology & carcinogenesis
biology.protein
Antibody
business
Subjects
Details
- ISSN :
- 19420870 and 19420862
- Database :
- OpenAIRE
- Journal :
- mAbs
- Accession number :
- edsair.doi.dedup.....d2ef59217946a86699660443f8903c45