Developmental Changes in the Processes Governing Oral Drug Absorption

Koning, Barbara A E de; Mooij, Miriam G.; Johnson, Trevor N.

doi:10.1007/978-1-4899-8011-3_3

Cited by 6 publications

(4 citation statements)

References 102 publications

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“…Furthermore, the small intestinal transit time is independent of material type and not associated with age (24,25), which concurs with those meta-analyses conducted by the developers of PK-Sim (8,31) and Simcyp (32). For a BCS class I drug with high permeability, even a slight change (increase or decrease) in the small intestinal transit time is not expected to have any significant impact on the extent of drug absorption, to say the least.…”

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confidence: 87%

Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Zheng

2014

AAPS J

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Abstract. Physiologically based pharmacokinetic (PBPK) modeling holds great promise for anticipating the quantitative changes of pharmacokinetics in pediatric populations relative to adults, which has served as a useful tool in regulatory reviews. Although the availability of specialized software for PBPK modeling has facilitated the widespread applications of this approach in regulatory submissions, challenges in the implementation and interpretation of pediatric PBPK models remain great, for which controversies and knowledge gaps remain regarding neonatal development of the gastrointestinal tract. The commentary highlights the similarities and differences in the gastrointestinal pH and transit time between neonates and adults from a PBPK modeling prospective. Understanding the similarities and differences in these physiological parameters governing oral absorption would promote good practice in the use of pediatric PBPK modeling to assess oral exposure and pharmacokinetics in neonates.KEY WORDS: gastric emptying; gastrointestinal pH; neonates; physiologically based pharmacokinetic modeling; small intestinal transit time.Although physiologically based pharmacokinetic (PBPK) modeling holds great promise for facilitating pediatric drug development and regulatory review, the implementation and interpretation of pediatric PBPK models continues to face challenges, in which controversies and knowledge gaps remain regarding neonatal development of the gastrointestinal tract. In this context, we would like to offer some comments on the recent article of Khalil and Läer (1). In the work by Khalil and Läer (1), inaccurate predictions of oral pharmacokinetics of sotalol, using two PBPK models, were observed in neonates. The authors ascribed the poor predictions to factors related to the absorption rather than elimination or distribution processes and highlighted the lack of many age-specific physiological alterations in the parameterization of the used pediatric absorption models. Apart from the ontogeny of intestinal transporters and drugmetabolizing enzymes, the authors argued that gastrointestinal pH profiles and transit time should be considered as agerelated physiological variables to improve the predictive power of pediatric PBPK models. In this commentary, we provide additional information to facilitate a better understanding of the similarities and differences in gastrointestinal physiology between neonates and adults, which are of critical importance when using PBPK models to simulate oral pharmacokinetics in neonates.Despite the neutral pH in newborn stomach at delivery has been well recognized (2,3), much of the literature is replete with contradictory information on the maturation of gastric pH during the neonatal period. Some suggested that the neonatal gastric pH is greater than 5, which is quite different from the adult level (4-6); but others believed that the gastric pH of neonates stays within a more acidic range of 2-3, which is similar to that of adults (7,8). Upon careful examination of the reported n...

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confidence: 87%

Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Zheng

2014

AAPS J

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“…Newborns and young infants are mainly fed with milk, whether it is breastmilk or different types of formulae, which can have an impact on several characteristics, including fed gastric pH. Studies have reported that pH values over 4 were detected more frequently in newborns and infants than in older children, mainly due to feeding patterns in this subpopulation and the high buffer capacity of breastmilk and formulae . Comparison of two separate studies (adults vs newborns) of continuously monitoring of the fed gastric pH showed that 2 h after a meal, higher fed gastric pH values (0.7–1.8 units) were found in newborns (2–15 days) .…”

Section: Physiological and Anatomical Changes In Paediatricsmentioning

confidence: 99%

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Guimarães

Statelova

Holm

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Hydroxybutyric acid plays an important role in guiding bone regeneration ( Kose et al, 2003 ).In our study, the contents of the above metabolites were lower in cage-reared ducks, which may be associated with the deterioration of the bone quality of these ducks. Moreover, the mutation of Cytochrome P450 3A4 ( CYP3A4 ) was found to be significantly associated with low bone mass ( Fukushima-Uesaka et al, 2004 ), and the CYP3A4 activity can be measured by the levels of 6beta-hydroxytestosterone ( de Koning et al, 2014 ). We found that ground ducks had a high level of 6beta-hydroxytestosterone, indicating that different rearing systems may affect the activity of CYP3A4, resulting in the difference in bone quality.…”

Section: Discussionmentioning

confidence: 99%

Untargeted metabolomics study on the effects of rearing ducks in cages on bone quality

et al. 2022

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The cage rearing model of the modern poultry industry makes the bones of birds more vulnerable to deterioration. In this study, at 8 wk of age, a total of 60 birds were randomly allocated to 2 groups, including the floor rearing group ( FRD ) and cage rearing group ( CRD ), and their body weight was measured every 2 wk. At the age of 20 wk, the tibia, femur, and humerus were collected from each group (n = 12) to determine the bone quality parameters such as weight, size, bone mineral density ( BMD ), breaking strength, cortical thickness, and area, ash content, calcium (Ca) content, and phosphorus (P) content. Meanwhile, the serum metabolome composition of both groups was detected by untargeted metabolome technology. The results showed that there were no significant differences in body weight, bone weight, and size between the 2 groups ( P > 0.05), but the humerus mineral density and the breaking strength, cortical bone thickness, cortical bone area percentage of tibia, femur, and humerus of CRD was significantly lower than those of FRD ( P < 0.05), indicating that the cage rearing system caused the deterioration of bone quality. Based on nontarget metabolomics, 49 metabolites were correlated with bone quality parameters, and 10 key metabolites were strongly correlated, including erucic acid, citric acid, and ketoleucine. In addition, the KEGG analysis showed that the caged system mainly perturbed amino acid metabolism, lipid metabolism, and energy metabolism, which led to changes in related metabolite levels, produced ROS, and altering energy supply, thus leading to a deterioration of bone quality of cage rearing ducks. Therefore, our findings were helpful to further understand the potential mechanism of the deterioration of duck bone quality in cage rearing system, provided a theoretical basis for reducing the occurrence of poultry osteoporosis, and ensuring the healthy development of poultry breeding.

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Developmental Changes in the Processes Governing Oral Drug Absorption

Cited by 6 publications

References 102 publications

Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Similarities and Differences in Gastrointestinal Physiology Between Neonates and Adults: a Physiologically Based Pharmacokinetic Modeling Perspective

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review

Untargeted metabolomics study on the effects of rearing ducks in cages on bone quality

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