Investigating oral absorption of carbamazepine in paediatric populations
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Autor:innen
Autor:in (Körperschaft)
Publikationsdatum
2017
Typ der Arbeit
Studiengang
Sammlung
Typ
01 - Zeitschriftenartikel, Journalartikel oder Magazin
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
The AAPS Journal
Themenheft
DOI der Originalpublikation
Reihe / Serie
Reihennummer
Jahrgang / Band
19
Ausgabe / Nummer
6
Seiten / Dauer
1864–1877
Patentnummer
Verlag / Herausgebende Institution
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Prediction 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.
Schlagwörter
BCS2, in vitro dissolution, oral absorption, PBPK modeling, pediatric biopharmaceutics
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
KOHLMANN, Philip, Cordula STILLHART, Neil PARROT und Martin KUENTZ, 2017. Investigating oral absorption of carbamazepine in paediatric populations. The AAPS Journal. 2017. Bd. 19, Nr. 6, S. 1864–1877. DOI 10.1208/s12248-017-0149-6. Verfügbar unter: http://hdl.handle.net/11654/25795