Cisapride disposition in neonates and infants: in vivo reflection of cytochrome P450 3A4 ontogeny

Kearns, Gregory L.; Robinson, P.; Wilson, John T.; Wilson-Costello, D.; Knight, G. R.; Ward, Robert M.; Anker, John N. van den

doi:10.1016/s0009-9236(03)00225-x

Cited by 64 publications

(25 citation statements)

References 36 publications

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“…Many studies described the hepatic ontogeny of CYP3A isoforms. CYP3A7, detected in fetal liver, was replaced by increasing protein and activity levels of CYP3A4 after birth (Lacroix et al, 1997;Kearns et al, 2003). In contrast, in our duodenal samples, after birth, CYP3A4 mRNA expression decreased significantly after the first month of life to reach adult levels.…”

Section: Discussioncontrasting

confidence: 61%

LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE

Fakhoury¹,

Litalien²,

Médard³

et al. 2005

Drug Metab Dispos

131

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ABSTRACT:Cytochromes P450 3A (CYP3A) and P-glycoprotein (P-gp) are mainly located in enterocytes and hepatocytes. The CYP3A/P-gp system contributes to the first-pass metabolism of many drugs, resulting in a limited bioavailability. During the neonatal period, a shift between CYP3A7, the fetal form, and CYP3A4 occurs in the liver, but data on the expression of the CYP3A/P-gp complex in the intestine are very limited. A total of 59 normal duodenal biopsies from white children aged 1 month to 17 years were studied. Localization of the proteins by immunohistochemistry analysis was performed using a polyclonal antibody, Nuage anti-CYP3A, and a monoclonal antibody, C494 anti-P-gp. The mRNA quantification was performed using highly specific real-time reverse transcription-polymerase chain reaction. Villin mRNA quantification was used for normalization. CYP3A protein was detected in all enterocytes in the samples from patients over 6 months of age, whereas it was not in younger samples. P-gp protein was expressed at the apical and upper lateral surfaces of the enterocytes. CYP3A isoforms and P-gp mRNA levels were highly variable. CYP3A4 and CYP3A5 mRNA levels were high during the first year of life and decreased with age, whereas CYP3A7 was detected at a low level in 64% of samples, whatever the age. P-gp mRNA expression level was also highly variable. Our results showed that neonates and infants had a significant expression of CYP3A and P-gp mRNA in the intestine, suggesting a different maturation profile of CYP3A and P-gp with age in the liver and the intestine.

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Section: Discussioncontrasting

confidence: 61%

LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE

Fakhoury¹,

Litalien²,

Médard³

et al. 2005

Drug Metab Dispos

131

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“…It was previously demonstrated that gastric empting rates increase during the first 7 days of life [12]. Correspondingly, time to maximum blood concentrations (T max ) have been observed to decrease during the first few weeks of life for some drugs like cisapride where T max at 42-54 weeks is nearly half-that observed at 28-36 weeks [13]. However, a recent meta-analysis challenges the theory that emptying matures as a function of age, proposing rather that the type of food administered to the child is more impactful [12,14].…”

Section: Peroral Administrationmentioning

confidence: 99%

Pharmacokinetic Considerations when Prescribing in Children

Eidelman

Abdel‐Rahman

2016

Int. J. Pharmacokinet.

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ReviewBefore prescribing, the pediatrician typically considers recommended dosing guidelines and issues related to safety. Rarely does (s)he consider the impact of normal growth and development on drug disposition and by extension drug action. This paper reviews how the processes of absorption, distribution, metabolism and elimination differ between healthy children and adults and briefly discusses considerations for medication prescribing in children where these processes are altered secondary to comorbidities.

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“…143 7 days after birth have only traces of CYP3A4, 144 whereas at the age of 1 month the enzyme activity constitutes only 30% to 40% of an adult's activity. 145 CYP3A4 activity can be assessed with the erythromycin respiratory test. 101 No polymorphism of the enzyme has been reported so far; nevertheless, sexdependent activity variations were observed (women have CYP3A4 activity 20% to 50% higher than men) regarding erythromycin, methylprednisolone, methadone, tacrolimus, modafinil, diltiazem, nifedipine, triazolam, cyclosporine, and verapamil (Table 12 146,147 ).…”

Section: Gastroesophageal Refluxmentioning

confidence: 99%

Advances of Molecular Clinical Pharmacology in Gastroenterology and Hepatology

Prandota¹

2010

American Journal of Therapeutics

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During developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin α-4 β-7, or IFN-β in some large-bowel diseases increased therapeutic efficacy. IFN-α used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.

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Cisapride disposition in neonates and infants: in vivo reflection of cytochrome P450 3A4 ontogeny

Cited by 64 publications

References 36 publications

LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE

LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE

Pharmacokinetic Considerations when Prescribing in Children

Advances of Molecular Clinical Pharmacology in Gastroenterology and Hepatology

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