Expression of intestinal drug transporter proteins and metabolic enzymes in neonatal and pediatric patients

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Fältnamn	Indikatorer	Metadata
000		03958naa a2200445 4500
001		oai:DiVA.org:uu-528223
003		SwePub
008		240517s2024 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5282232 URI
024	7	a https://doi.org/10.1016/j.ijpharm.2024.1239622 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a de Waal, Tomu Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.4 aut
245	1 0	a Expression of intestinal drug transporter proteins and metabolic enzymes in neonatal and pediatric patients
264	1	b Elsevier,c 2024
338		a print2 rdacarrier
520		a The development of pediatric oral drugs is hampered by a lack of predictive simulation tools. These tools, in turn, require data on the physiological variables that influence oral drug absorption, including the expression of drug transporter proteins (DTPs) and drug-metabolizing enzymes (DMEs) in the intestinal tract. The expression of hepatic DTPs and DMEs shows age-related changes, but there are few data on protein levels in the intestine of children. In this study, tissue was collected from different regions of the small and large intestine from neonates (i.e., surgically removed tissue) and from pediatric patients (i.e., gastroscopic duodenal biopsies). The protein expression of clinically relevant DTPs and DMEs was determined using a targeted mass spectrometry approach. The regional distribution of DTPs and DMEs was similar to adults. Most DTPs, with the exception of MRP3, MCT1, and OCT3, and all DMEs showed the highest protein expression in the proximal small intestine. Several proteins (i.e., P-gp, ASBT, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and UGT1A1) showed an increase with age. Such increase appeared to be even more pronounced for DMEs. This exploratory study highlights the developmental changes in DTPs and DMEs in the intestinal tract of the pediatric population. Additional evaluation of protein function in this population would elucidate the implications of the presented changes in protein expression on absorption of orally administered drugs in neonates and pediatric patients.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng
653		a Drug transporter proteins
653		a Metabolic enzymes
653		a Pediatric patients
653		a Neonates
653		a Gastrointestinal ontogeny
700	1	a Handin, Niklasu Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)nikha230
700	1	a Brouwers, Joachimu Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.4 aut
700	1	a Miserez, Marcu Univ Hosp Leuven, Dept Abdominal Surg, Leuven, Belgium.4 aut
700	1	a Hoffman, Ilseu Univ Hosp Leuven, Pediat Gastroenterol Hepatol & Nutr, Leuven, Belgium.4 aut
700	1	a Rayyan, Maissau Univ Hosp Leuven, Neonatal Intens Care Unit, Leuven, Belgium.4 aut
700	1	a Artursson, Peru Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)perartur
700	1	a Augustijns, Patricku Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.4 aut
710	2	a Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.b Institutionen för farmaci4 org
773	0	t International Journal of Pharmaceuticsd : Elsevierg 654q 654x 0378-5173x 1873-3476
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-528223
856	4 8	u https://doi.org/10.1016/j.ijpharm.2024.123962

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By the author/editor: de Waal, Tom; Handin, Niklas; Brouwers, Joachi ...; Miserez, Marc; Hoffman, Ilse; Rayyan, Maissa; show more...; Artursson, Per; Augustijns, Patr ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Pediatrics

Articles in the publication: International Jo ...

By the university: Uppsala University

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