Ontogeny of oral drug absorption processes in children

Mooij, Miriam G.; Koning, Barbara A E de; Huijsman, Mark L; Wildt, Saskia N. de

doi:10.1517/17425255.2012.698261

Cited by 78 publications

(71 citation statements)

References 99 publications

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“…Understanding changes in gastric emptying with age is important both clinically in terms of the pathophysiology of disease and for predicting the absorption of orally administered drugs 32. Gastric emptying is a primary determinant of the rate at which drugs are presented to the small intestinal mucosa for absorption and, along with a multitude of other age related changes, may influence the design of suitable dosage forms for administration to neonates and infants.…”

Section: Introductionmentioning

confidence: 99%

Does age affect gastric emptying time? A model‐based meta‐analysis of data from premature neonates through to adults

Bonner

Vajjah

Abduljalil

et al. 2015

Biopharm & Drug Disp

124

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Purpose. Gastric emptying (GE) is often reported to be slower and more irregular in premature neonates than in older children and adults. The aim of this study was to investigate the impact of age and other covariates on the rate of GE. Methods. The effect of age on the mean gastric residence times (MGRT) of liquid and solid food was assessed by analysing 49 published studies of 1457 individuals, aged from 28 weeks gestation to adults. The data were modelled using the nonlinear mixed‐effects approach within NONMEM version 7.2 (ICON, Dublin, Ireland), with evaluation of postnatal age, gestational age and meal type as covariates. A double Weibull function was selected as a suitable model since it could account for the typical biphasic nature of GE. Results. Age was not a significant covariate for GE but meal type was. Aqueous solutions were associated with the fastest emptying time (mean simulated gastric residence time of 45 min) and solid food was associated with the slowest (98 min). Conclusions. These findings challenge the assertion that GE is different in neonates, as compared with older children and adults due to age, and they reinforce the significance of food type in modulating GE. © 2015 The Authors. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.

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Section: Introductionmentioning

confidence: 99%

Does age affect gastric emptying time? A model‐based meta‐analysis of data from premature neonates through to adults

Bonner

Vajjah

Abduljalil

et al. 2015

Biopharm & Drug Disp

124

View full text Add to dashboard Cite

show abstract

“…Consequently, their applicability towards pediatric populations, who are developmentally distinct in terms of gastrointestinal anatomy/physiology, remains questionable. Of most interest are children belonging to the youngest age groups (i.e., neonates and infants) who display the greatest developmental differences in comparison to adults (6,7).…”

Section: Introductionmentioning

confidence: 99%

Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

2015

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“…Some PEPT1 substrates are dosed to children even very early in life. Considering the wide age-related variation in the processes affecting oral drug absorption-including gastric pH, gastric motility, and drug metabolizing enzyme activity-age-related changes in membrane transporters are also very likely (Mooij et al, 2012). A previous study by our group Mooij et al (2014) showed transporter-dependent maturation in gene expression in young infants for MDR1, MRP2, and OATP2B1, but overall data on the intestinal expression of membrane transporters during growth and development are very scarce (Brouwer et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Human Intestinal PEPT1 Transporter Expression and Localization in Preterm and Term Infants

Mooij

Koning

Lindenbergh-Kortleve

et al. 2016

Drug Metabolism and Disposition

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The intestinal influx oligopeptide transporter peptide transporter 1 (PEPT1) (SLC15A1) is best known for nutrient-derived di-and tripeptide transport. Its role in drug absorption is increasingly recognized. To better understand the disposition of PEPT1 substrate drugs in young infants, we studied intestinal PEPT1 mRNA expression and tissue localization across the pediatric age range. PEPT1 mRNA expression was determined using real-time reversetranscription polymerase chain reaction in small intestinal tissues collected from surgical procedures (neonates and infants) or biopsies (older children and adolescents). PEPT1 mRNA relative to villin mRNA expression was compared between neonates/infants and older children/adolescents. PEPT1 was visualized in infant tissue using immunohistochemical staining. Other transporters [multidrug resistance protein 1 (MDR1), multidrug resistance-like protein 2 (MRP2), and organic anion transporter polypeptide 2B1 (OATP2B1)] were also stained to describe the localization in relation to PEPT1. Twenty-six intestinal samples (n = 20 neonates/infants, n = 2 pediatric, n = 4 adolescents) were analyzed. The young infant samples were collected at a median (range) gestational age at birth of 29.2 weeks (24.7-40) and postnatal age of 2.4 weeks (0-16.6). The PEPT1 mRNA expression of the neonates/infants was only marginally lower (0.8-fold) than the older children (P < 0.05). Similar and clear apical PEPT1 and MRP2 staining, apical and lateral MDR1 staining, and intraepithelial OATP2B1 staining at the basolateral membrane of the enterocyte were detected in 12 infant and 2 adolescent samples. Although small intestinal PEPT1 expression tended to be lower in neonates than in older children, this difference is small and tissue distribution is similar. This finding suggests similar oral absorption of PEPT1 substrates across the pediatric age range.

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Ontogeny of oral drug absorption processes in children

Cited by 78 publications

References 99 publications

Does age affect gastric emptying time? A model‐based meta‐analysis of data from premature neonates through to adults

Does age affect gastric emptying time? A model‐based meta‐analysis of data from premature neonates through to adults

Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

Human Intestinal PEPT1 Transporter Expression and Localization in Preterm and Term Infants

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