title: In vitro gastrointestinal model (TIM) with predictive power, even for infants and children?
abstract: There is a need for information on the bioavailability in pediatric patients of drugs from manipulated dosage forms when applied in combination with food and/or co-medication under realistic daily practice circumstances. We describe the development, validation and application of a dynamic, computer-controlled in vitro system mimicking the conditions in the upper gastrointestinal tract of neonates, infants and toddlers: TIMpediatric. Paracetamol and diclofenac in age-related food matrices and with esomeprazole co-medication were tested. The experiments showed relevant results on the impact of drug manipulation and co-medication on the availability for absorption of active compounds. Without ethical constraints, alternative approaches for oral dosing and new pediatric formulations can be studied in TIMpediatric with a high predictive value.
authors.affiliation: TNO, P.O. Box 360, 3700 AJ Zeist, The Netherlands. Electronic address: rob.havenaar@tno.nl.
authors.forename: Robert
authors.initials: R
authors.lastname: Havenaar
authors.forename: Bart
authors.initials: B
authors.lastname: Anneveld
authors.forename: Lidwien M
authors.initials: LM
authors.lastname: Hanff
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.forename: Barbara A E
authors.initials: BA
authors.lastname: de Koning
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mooij
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Lelieveld
authors.forename: Mans
authors.initials: M
authors.lastname: Minekus
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics; D001682:Biological Availability; D002648:Child; D004008:Diclofenac / Q000493:pharmacokinetics; D064098:Esomeprazole / Q000493:pharmacokinetics; D041981:Gastrointestinal Tract / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008954:Models, Biological
chemical_list: D004008:Diclofenac; D000082:Acetaminophen; D064098:Esomeprazole
keywords: Bioaccessibility; Drug handling; In vitro gastrointestinal model; Pediatric drug