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dc.contributor.authorKohlmann, Philip
dc.contributor.authorStillhart, Cordula
dc.contributor.authorParrot, Neil
dc.contributor.authorKuentz, Martin
dc.date.accessioned2018-01-10T09:28:28Z
dc.date.available2018-01-10T09:28:28Z
dc.date.issued2017
dc.identifier.doi10.1208/s12248-017-0149-6
dc.identifier.urihttp://hdl.handle.net/11654/25795
dc.description.abstractPrediction of the pharmacokinetics of orally administered drugs in children is of importance to optimize the efficacy and safety of pediatric medicines. Physiologically based pharmacokinetic (PBPK) models can be helpful for this purpose. However, application of these tools is limited by significant knowledge gaps regarding the physiological and anatomical changes which occur with age. This study aimed at investigating the age-dependent differences in oral absorption of a poorly soluble model compound, carbamazepine (CBZ) in children, infants, and neonates. We developed an oral absorption model in GastroPlus® and, after evaluation of the PBPK model for adults, extrapolation to younger ages was verified with clinical data and sensitivity analyses were applied for uncertain model parameters. We found that age-based scaling of physiological parameters, with clearance in particular, was important to obtain adequate simulation results. The sensitivity analysis revealed that CBZ absorption was influenced by solubility, particle radius, and small intestinal transit time depending on the pediatric age group and CBZ dose. However, in vitro dissolution testing using proposed pediatric biorelevant media suggested no major age dependency of dissolution kinetics. Such better understanding of oral absorption in pediatric patients is required to improve the prediction of exposure in children and the confidence in oral biopharmaceutical tools.
dc.description.urihttps://link.springer.com/article/10.1208%2Fs12248-017-0149-6
dc.language.isoen_US
dc.relation.ispartofThe AAPS Journal
dc.accessRightsAnonymous
dc.subjectBCS2
dc.subjectin vitro dissolution
dc.subjectoral absorption
dc.subjectPBPK modeling
dc.subjectpediatric biopharmaceutics
dc.titleInvestigating oral absorption of carbamazepine in paediatric populations
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume19
dc.issue6
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandYes
fhnw.pagination1864–1877
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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