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dc.contributor.authorVilliger, Angela
dc.contributor.authorStillhart, Cordula
dc.contributor.authorParrot, Neil
dc.contributor.authorKuentz, Martin
dc.date.accessioned2016-12-13T11:40:28Z
dc.date.available2016-12-13T11:40:28Z
dc.date.issued2016-07-08
dc.identifier.doi10.1208/s12248-016-9896-z
dc.identifier.urihttp://hdl.handle.net/11654/23693
dc.description.abstractPaediatric pharmaceutics has become an important topic, but currently, there is an incomplete knowledge of paediatric gastrointestinal physiology and adequate biopharmaceutical tools still have to be developed. The present study aimed to increase the understanding of oral drug absorption in paediatric populations by using physiologically based pharmacokinetic (PBPK) modelling and in vitro dissolution testing. The oral absorption of two model compounds, sotalol and paracetamol, was studied by collection of reported pharmacokinetic profiles from adult and paediatric subjects. A PBPK model based on input parameters collected from the literature was first developed and validated in adults before being extrapolated to paediatric age groups. The accuracy of the model simulations was assessed by comparison to the observed pharmacokinetic profiles, and in the case of discrepancy, further investigations were made via parameter sensitivity analysis and in vitro dissolution testing. The PBPK models accurately predicted sotalol and paracetamol exposure in adult populations. An accurate simulation was also obtained after model extrapolation to children older than 2 years of age. However, the simulation in infants and newborns resulted in a discrepancy, which was further analysed. Dissolution testing suggested no significant difference in the drug release rate between paediatric and adult age groups. In contrast, mean gastric emptying time seemed to be underestimated in infants and newborns, and optimisation of this input parameter improved the prediction of the model. Considering age-specific differences in gastrointestinal tract physiology should improve prediction of drug absorption in paediatric patients.
dc.description.urihttp://link.springer.com/article/10.1208%2Fs12248-016-9896-z
dc.language.isoen
dc.relation.ispartofThe AAPS Journal
dc.accessRightsAnonymous
dc.subjectin vitro dissolution
dc.subjectmean gastric transit time
dc.subjectoral drug absorption
dc.titleUsing Physiologically Based Pharmacokinetic (PBPK) Modelling to Gain Insights into the Effect of Physiological Factors on Oral Absorption in Paediatric Populations
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume18
dc.issue4
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination933-947
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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