Bile Acid Metabolism During Development

Karpen, Heidi; Karpen, Saul J.

doi:10.1016/b978-0-323-35214-7.00095-0

Cited by 6 publications

(5 citation statements)

References 202 publications

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“…Active transport of bile salts in the ileum is contingent on the expression of the ASBT, which is active at birth in the guinea pig (Heubi and Fondacaro, 1982), but not until weaning in the rat and rabbit (Little and Lester, 1980;Barnard et al, 1985;Moyer et al, 1988;Shneider et al, 1997). A detailed review of enterohepatic bile circulation is beyond the scope of this review, but the development and activity of intestinal transporters in general, in addition to hepatic bile production and conjugation reactions, can contribute to drug and/or chemical disposition, as has been previously reviewed (Staggers et al, 1982;Pácha, 2000;Drozdowski et al, 2010;Brouwer et al, 2015;Karpen and Karpen, 2017). Thus, for lipophilic chemicals and drugs that are primarily excreted through the bile, the physiologic maturation of these pathways must be considered for both human neonates and species used for toxicity testing.…”

Section: Excretionmentioning

confidence: 88%

“…As has been extensively reviewed, the bile salt pool of neonates contributes to fat absorption, elimination of bilirubin, GIT maturation, and successful bacterial colonization of the GIT (Skinner, 2014;Cashore, 2017). Although much of the literature has focused on bile production and conjugation in the fetal and neonatal liver, there are elements of GIT development that also contribute to production and enterohepatic circulation of bile salts, as has been reviewed (Ridlon et al, 2014;Karpen and Karpen, 2017). For example, the production of secondary bile acids requires enzymatic modification by colonic bacteria, which develop in parallel with the microbiome postnatally.…”

Section: Bile Salt Impact On Fat Absorptionmentioning

confidence: 99%

“…In contrast to the sparse data for intestinal drug transporters, there is a robust understanding of the ontogeny of sugar, amino acid, vitamin, and inorganic phosphate transport for neonatal humans and animals, largely driven by the needs of clinical nutrition to optimize infant feeding formulations and strategies, as reviewed previously (Buddington, 1992(Buddington, , 1994Pácha, 2000;Boudry et al, 2010;Drozdowski et al, 2010;Poquet and Wooster, 2016). In addition, the development of specific bile transporters, such as the apical sodium bile transporter in the ileum, is well described for humans and rats (Little and Lester, 1980;Staggers et al, 1982;Karpen and Karpen, 2017).…”

Section: Intestinal Transportersmentioning

confidence: 99%

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Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

et al. 2018

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A thorough knowledge of the newborn (age, birth to 1 month postpartum) infant's gastrointestinal tract (GIT) is critical to the evaluation of the absorption, distribution, metabolism, and excretion (ADME) of orally administered drugs in this population. Developmental changes in the GIT during the newborn period are important for nutrient uptake as well as the disposition of orally administered medications. Some aspects of gastrointestinal function do not mature until driven by increased dietary complexity and nutritional demands later in the postnatal period. The functionalities present at birth, and subsequent maturation, can also impact the ADME parameters of orally administered compounds. This review will examine some specific contributors to the ADME processes in human neonates, as well as what is currently understood about the drivers for their maturation. Key species differences will be highlighted, with a focus on laboratory animals used in juvenile toxicity studies. Because of the gaps and inconsistencies in our knowledge, we will also highlight areas where additional study is warranted to better inform the appropriate use of medicines specifically intended for neonates.

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Section: Excretionmentioning

confidence: 88%

Section: Bile Salt Impact On Fat Absorptionmentioning

confidence: 99%

Section: Intestinal Transportersmentioning

confidence: 99%

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Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

et al. 2018

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“…In the intestine, efflux transporters limiting drug absorption are P-gp, MRP2, and BCRP. Drug intestinal absorption is mainly performed with OATP1A2, OATP2B1, and peptide transporter 1 (PEPT1) [ 44 ].…”

Section: General Considerations On Neonate’s Pharmacokineticsmentioning

confidence: 99%

Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants

et al. 2023

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Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial resistance precipitates the growth of the use of antibiotics of the Watch (second, third, and fourth generations of cephalosporines, carbapenems, macrolides, glycopeptides, rifamycins, fluoroquinolones) and Reserve groups (fifth generation of cephalosporines, oxazolidinones, lipoglycopeptides, fosfomycin), which are associated with a less clinical experience and higher risks of toxic reactions. A proper dosing regimen is essential for effective and safe antibiotic therapy, but its choice in neonates is complicated with high variability in the maturation of organ systems affecting drug absorption, distribution, metabolism, and excretion. Changes in antibiotic pharmacokinetic parameters result in altered efficacy and safety. Population pharmacokinetics can help to prognosis outcomes of antibiotic therapy, but it should be considered that the neonatal population is heterogeneous, and this heterogeneity is mainly determined by gestational and postnatal age. Preterm neonates are common in clinical practice, and due to the different physiology compared to the full terms, constitute a specific neonatal subpopulation. The objective of this review is to summarize the evidence about the developmental changes (specific for preterm and full-term infants, separately) of pharmacokinetic parameters of antibiotics used in neonatal intensive care units.

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“…Bile acids are found predominantly in the bile of mammals and other vertebrates as oxygenated metabolites of steroids [1,2]. They are classified in two groups: primary bile acids (cholic, CA, and chenodeoxycholic, CDCA) which are synthesized by the liver, and secondary bile acids which are obtained through enterobacterial metabolism of primary bile acids, such as deoxycholic (DCA), lithocholic (LCA), and hyodeoxycholic (HDCA) acids (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Bile acids: Lipase-catalyzed synthesis of new hyodeoxycholic acid derivatives

et al. 2018

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In this work we present an efficient, environmentally friendly approach to the synthesis of a series of hyodeoxycholic acid derivatives applying Biocatalysis. Fifteen acetyl and ester derivatives, twelve of them new, were obtained through an enzymatic strategy in a fully regioselective way and in very good to excellent yield. In order to find the optimal reaction conditions, the influence of several parameters such as enzyme source, alcohol or acylating agent:substrate ratio, enzyme:substrate ratio, temperature and reaction solvent was considered. The excellent results obtained made this procedure very efficient, particularly considering the low amount of enzyme required. In addition, this methodology uses mild reaction conditions and has reduced environmental impact, making biocatalysis a suitable way to obtaining these bile acids derivatives.

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Bile Acid Metabolism During Development

Cited by 6 publications

References 202 publications

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants

Bile acids: Lipase-catalyzed synthesis of new hyodeoxycholic acid derivatives

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