Successful extrapolation of paracetamol exposure from adults to infants after oral administration of a paediatric aqueous suspension is highly dependent on the study dosing conditions
| Autor: | René Holm, Nikoletta Fotaki, Maria Vertzoni, Marina Statelova, Christos Reppas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pediatrics
paracetamol Administration Oral Datasets as Topic Pharmaceutical Science 030226 pharmacology & pharmacy Biopharmaceutics Food-Drug Interactions 0302 clinical medicine Oral administration oral absorption Body Size Medicine Child media_common infants Age Factors 3. Good health Drug development Child Preschool 030220 oncology & carcinogenesis Administration Intravenous physiologically based pharmacokinetic (PBPK) modeling Adult Drug Physiologically based pharmacokinetic modelling medicine.medical_specialty Adolescent Metabolic Clearance Rate media_common.quotation_subject Biological Availability Models Biological 03 medical and health sciences Suspensions Pharmacokinetics Health Sciences food effect Humans Computer Simulation Dosing Acetaminophen Dose-Response Relationship Drug Gastric emptying business.industry Infant Bioavailability Gastrointestinal Absorption Επιστήμες Υγείας business |
| Zdroj: | Statelova, M, Holm, R, Fotaki, N, Reppas, C & Vertzoni, M 2020, ' Successful Extrapolation of Paracetamol Exposure from Adults to Infants After Oral Administration of a Pediatric Aqueous Suspension Is Highly Dependent on the Study Dosing Conditions ', AAPS Journal, vol. 22, no. 6, 126 . https://doi.org/10.1208/s12248-020-00504-6 The AAPS Journal |
| Popis: | Extending licensed drug use to the pediatric population has become an essential part of the drug development process. Nonetheless, ethical concerns limit clinical testing in pediatric populations and data collected from oral bioavailability and food effect studies in adults are often extrapolated to the target pediatric (sub)populations. However, based on published information, food effects on drug absorption in infants may not be adequately evaluated by data collected in adults. In the present study, a physiologically based pharmacokinetic (PBPK) approach for modeling paracetamol suspension data collected in adults was proposed with the ultimate aim to investigate whether extrapolation to infants is substantially affected by the dosing conditions applied to adults. The development of the PBPK model for adults was performed using GastroPlus™ V9.7, and after scaling to infants considering physiological, anatomical, and drug clearance changes, extrapolation of the different dosing conditions was performed by applying dosing conditions dependent on changes on the paracetamol gastric emptying process. Successful simulations of previously observed plasma concentration levels in infants were achieved when extrapolating from fasted and infant formula–fed conditions data. Data collected following the reference meal appeared less useful for simulating paracetamol suspension performance in infants. The proposed methodology deserves further evaluation using high-quality clinical data both in adults and in infants. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|