FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567322443> ?p ?o ?g. }

• W1567322443 endingPage "912" @default.
• W1567322443 startingPage "910" @default.
• W1567322443 abstract "Infants and children are unique patient populations compared with adults as they not only differ physiologically and anatomically but also experience rapid changes in growth and development over the course of their childhood. These dynamic and variable developmental changes can have major impact on the pharmacokinetic and pharmacodynamic profile of a drug from its absorption, distribution, metabolism and elimination (ADME) properties to its effects 1. Since oral administration is one of the primary routes for giving a drug to children, many studies have been implemented to provide evidence for developmental differences in the absorption of drugs 1, 2. As is well known, the bioavailability of orally administered drugs is regulated by various metabolic enzymes and transporters expressed in the small intestine. Therefore, the developmental changes in activity of metabolic enzymes and transporters could explain developmental differences in absorption. To date, several studies have characterized the ontogeny of metabolic enzymes in tissues including the small intestine 1-3. However, there is little information on the ontogeny of drug transporters in the human intestine. P-glycoprotein (MDR1/ABCB1), an ATP-binding cassette transporter, located in the small intestine mediates the efflux of substrates from the epithelial cells to the intestinal lumen 4. Thus, the inter-individual variability in the expression of intestinal ABCB1 is an important factor which determines the bioavailability of ABCB1 substrates, as has been shown for tacrolimus 5. Since many drugs used in neonates, infants and children are substrates of ABCB1, it is important to characterize the effects of developmental changes of intestinal ABCB1 on drug disposition in children 1, 2. Here, we evaluate ABCB1 mRNA expression patterns in human small intestine tissues collected from children to provide fundamental information on the age-dependent expression. mRNA expression data were obtained as part of a previous study at Kyoto University Hospital, Japan 5. In short, 206 paediatric patients undergoing living donor liver transplantation were enrolled in the study. All mucosal specimens of the upper jejunum were obtained from a part of the Roux-en-Y limb for biliary reconstruction or around the bile drainage tube during surgery. Samples were immediately frozen in liquid nitrogen and stored at −80°C until analysis. ABCB1 mRNA expression was determined by quantitative RT-PCR as previously described 5. The amount was determined with a standard curve generated using known amounts of standard plasmid DNA. To verify the quality of the total cellular RNA extracted, GAPDH mRNA expression was also quantified as an internal standard. Demographics of patients were as follows: median age (range) 1.27 years (62 days–18.9 years), median body weight (range) 8.5 kg (3.7–70 kg), 85 male and 121 female patients. The study was approved by the Institutional Review Board and all participants, patients and/or care givers, gave written informed consent or assent. Large inter-individual variability in intestinal ABCB1 expression was observed across all ages (Figure 1). Over the studied age range from 62 days to 18.9 years, no clear maturation trajectory of ABCB1 expression was observed. This may indicate that the expression of intestinal ABCB1 has reached at the certain level by at least 2 months after the birth. A most recent report showed no significant difference in intestinal ABCB1 mRNA expression between neonates and adults 6. Although our data are not completely comparable due to the lack of samples in neonates, the report indirectly supports our observation. On the other hand, there is an earlier study demonstrating a very weak or no expression of ABCB1 in the fetal intestine 7. Furthermore, a study using enterocyte cell lines demonstrated that breast milk induces ABCB1 expression in a dose- and time-dependent manner 8. An animal study also demonstrated that the ABCB1 expression in the small intestine of neonatal rodents dramatically increased shortly after initiation of breastfeeding 8. Since lactation is generally started right after the birth, the expression of intestinal ABCB1 is anticipated to initiate at the same time and rapidly reach levels comparable with those seen in adults. Age related changes of intestinal ABCB1 mRNA expression. Data represent individual ABCB1 mRNA expression As with the small intestine, developmental changes in hepatic ABCB1 expression has been of great interest as an important consideration in the development of age-appropriate dosing strategies. In a recent preliminary report, it was noted that hepatic ABCB1 mRNA expression in fetuses, neonates, infants and children was 25–60-fold lower compared with adult values 9. In addition, in a recent review article, Klaassen & Aleksunes also reported that mRNA expression of ABCB1 in perinatal human liver samples was very low and gradually increased over time until the age of 7 years 10. The maturation pattern of ABCB1 expression is most likely organ-specific and needs to be studied in each organ. In conclusion, this analysis suggests that the maturation of intestinal ABCB1 mRNA expression is completed relatively soon after birth. This finding contributes to an improved understanding of the age dependent maturation of ABCB1 transporter mRNA expression and its potential effect on the disposition of drug substrates. All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf and declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. We thank the members of Department of Pharmacy, Kyoto University Hospital and surgeons of Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan for providing the clinical samples and information. This work was supported in part by a Funding Program for Next Generation World-Leading Researchers (NEXT Program: LS073) initiated by the Council for Science and Technology Policy of the Japan Society for the Promotion of Science of Japan. TM was supported by the Japan Research Foundation for Clinical Pharmacology." @default.
• W1567322443 created "2016-06-24" @default.
• W1567322443 creator A5004410085 @default.
• W1567322443 creator A5010169211 @default.
• W1567322443 creator A5013881333 @default.
• W1567322443 creator A5016058238 @default.
• W1567322443 creator A5040060343 @default.
• W1567322443 creator A5056835579 @default.
• W1567322443 creator A5072168969 @default.
• W1567322443 date "2014-04-22" @default.
• W1567322443 modified "2023-10-05" @default.
• W1567322443 title "Developmental trajectory of intestinal MDR1/ABCB1 mRNA expression in children" @default.
• W1567322443 cites W1605785874 @default.
• W1567322443 cites W1988234169 @default.
• W1567322443 cites W1988703513 @default.
• W1567322443 cites W2028890879 @default.
• W1567322443 cites W2071454976 @default.
• W1567322443 cites W2090632754 @default.
• W1567322443 cites W2122527560 @default.
• W1567322443 doi "https://doi.org/10.1111/bcp.12211" @default.
• W1567322443 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4004414" @default.
• W1567322443 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23879365" @default.
• W1567322443 hasPublicationYear "2014" @default.
• W1567322443 type Work @default.
• W1567322443 sameAs 1567322443 @default.
• W1567322443 citedByCount "19" @default.
• W1567322443 countsByYear W15673224432014 @default.
• W1567322443 countsByYear W15673224432015 @default.
• W1567322443 countsByYear W15673224432016 @default.
• W1567322443 countsByYear W15673224432017 @default.
• W1567322443 countsByYear W15673224432018 @default.
• W1567322443 countsByYear W15673224432019 @default.
• W1567322443 countsByYear W15673224432020 @default.
• W1567322443 countsByYear W15673224432021 @default.
• W1567322443 countsByYear W15673224432022 @default.
• W1567322443 crossrefType "journal-article" @default.
• W1567322443 hasAuthorship W1567322443A5004410085 @default.
• W1567322443 hasAuthorship W1567322443A5010169211 @default.
• W1567322443 hasAuthorship W1567322443A5013881333 @default.
• W1567322443 hasAuthorship W1567322443A5016058238 @default.
• W1567322443 hasAuthorship W1567322443A5040060343 @default.
• W1567322443 hasAuthorship W1567322443A5056835579 @default.
• W1567322443 hasAuthorship W1567322443A5072168969 @default.
• W1567322443 hasBestOaLocation W15673224431 @default.
• W1567322443 hasConcept C104317684 @default.
• W1567322443 hasConcept C112705442 @default.
• W1567322443 hasConcept C133936738 @default.
• W1567322443 hasConcept C134018914 @default.
• W1567322443 hasConcept C149011108 @default.
• W1567322443 hasConcept C181389837 @default.
• W1567322443 hasConcept C2777882243 @default.
• W1567322443 hasConcept C2778707650 @default.
• W1567322443 hasConcept C2780035454 @default.
• W1567322443 hasConcept C37291498 @default.
• W1567322443 hasConcept C501593827 @default.
• W1567322443 hasConcept C55493867 @default.
• W1567322443 hasConcept C64903051 @default.
• W1567322443 hasConcept C69366308 @default.
• W1567322443 hasConcept C86803240 @default.
• W1567322443 hasConcept C98274493 @default.
• W1567322443 hasConceptScore W1567322443C104317684 @default.
• W1567322443 hasConceptScore W1567322443C112705442 @default.
• W1567322443 hasConceptScore W1567322443C133936738 @default.
• W1567322443 hasConceptScore W1567322443C134018914 @default.
• W1567322443 hasConceptScore W1567322443C149011108 @default.
• W1567322443 hasConceptScore W1567322443C181389837 @default.
• W1567322443 hasConceptScore W1567322443C2777882243 @default.
• W1567322443 hasConceptScore W1567322443C2778707650 @default.
• W1567322443 hasConceptScore W1567322443C2780035454 @default.
• W1567322443 hasConceptScore W1567322443C37291498 @default.
• W1567322443 hasConceptScore W1567322443C501593827 @default.
• W1567322443 hasConceptScore W1567322443C55493867 @default.
• W1567322443 hasConceptScore W1567322443C64903051 @default.
• W1567322443 hasConceptScore W1567322443C69366308 @default.
• W1567322443 hasConceptScore W1567322443C86803240 @default.
• W1567322443 hasConceptScore W1567322443C98274493 @default.
• W1567322443 hasIssue "5" @default.
• W1567322443 hasLocation W15673224431 @default.
• W1567322443 hasLocation W15673224432 @default.
• W1567322443 hasLocation W15673224433 @default.
• W1567322443 hasLocation W15673224434 @default.
• W1567322443 hasOpenAccess W1567322443 @default.
• W1567322443 hasPrimaryLocation W15673224431 @default.
• W1567322443 hasRelatedWork W2005031996 @default.
• W1567322443 hasRelatedWork W2030193124 @default.
• W1567322443 hasRelatedWork W2030240071 @default.
• W1567322443 hasRelatedWork W2083913321 @default.
• W1567322443 hasRelatedWork W2111483198 @default.
• W1567322443 hasRelatedWork W2153831826 @default.
• W1567322443 hasRelatedWork W2335687845 @default.
• W1567322443 hasRelatedWork W2616206605 @default.
• W1567322443 hasRelatedWork W2681933021 @default.
• W1567322443 hasRelatedWork W2943083791 @default.
• W1567322443 hasVolume "77" @default.
• W1567322443 isParatext "false" @default.
• W1567322443 isRetracted "false" @default.
• W1567322443 magId "1567322443" @default.
• W1567322443 workType "article" @default.