Abstract
The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during fetal life and in the perinatal period are at the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs - total cytochrome P450 content in the fetal liver being 30% to 60% of adult values - may explain the prolonged actions of many drugs in the newborn, as well as less their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the fetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.
Keywords: Drugs, hepatotoxicity, human newborn, DILI, cytochrome P-450, liver, perinatal, glutathione, activation, metabolites.
Current Medicinal Chemistry
Title:A Developmental Approach to Drug-induced Liver Injury in Newborns and Children
Volume: 19 Issue: 27
Author(s): G. Faa, J. Ekstrom, M. Castagnola, Y. Gibo, G. Ottonello and V. Fanos
Affiliation:
Keywords: Drugs, hepatotoxicity, human newborn, DILI, cytochrome P-450, liver, perinatal, glutathione, activation, metabolites.
Abstract: The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during fetal life and in the perinatal period are at the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs - total cytochrome P450 content in the fetal liver being 30% to 60% of adult values - may explain the prolonged actions of many drugs in the newborn, as well as less their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the fetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.
Export Options
About this article
Cite this article as:
Faa G., Ekstrom J., Castagnola M., Gibo Y., Ottonello G. and Fanos V., A Developmental Approach to Drug-induced Liver Injury in Newborns and Children, Current Medicinal Chemistry 2012; 19 (27) . https://dx.doi.org/10.2174/092986712803306385
DOI https://dx.doi.org/10.2174/092986712803306385 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Drug-Induced Pulmonary Hypertension in Newborns: A Review.
Current Vascular Pharmacology Safety of Therapeutics Used in Management of Patent Ductus Arteriosus in Preterm Infants
Current Drug Safety Development of Urinary Assay Methods for the Estimation of Paracetamol Glucuronide and Paracetamol Sulphate in Preterm Neonates with Patent Ductus Arteriosus
Current Chromatography Neonatal Ultrasound in Transport
Current Pediatric Reviews Respiratory Syncytial Virus (RSV) Prevention and Treatment: Past, Present, and Future
Cardiovascular & Hematological Agents in Medicinal Chemistry Coarctation of the Aorta - An Evolution of Therapeutic Options
Current Cardiology Reviews Cardiovascular Imaging for Guiding Interventional Therapy in Structural Heart Diseases
Current Medical Imaging Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility
Current Pharmaceutical Design Complications of the Chest Wall and the Respiratory System After Surgery and Functional Performance
Current Respiratory Medicine Reviews The Impact of Hypothermia on the Pharmacokinetics of Drugs Used in Neonates and Young Infants
Current Pharmaceutical Design Bronchopulmonary Dysplasia: An Imbalance of Inflammation
Current Respiratory Medicine Reviews Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defects
Current Drug Metabolism Steroids and Vasopressor-Resistant Hypotension in Preterm Infants
Current Pediatric Reviews Therapeutic Targets for Management of Periodontitis and Diabetes
Current Pharmaceutical Design Troponin in Newborns and Pediatric Patients
Cardiovascular & Hematological Agents in Medicinal Chemistry Postnatal Growth Restriction in Preterm Infants: A Major Impact of Nutritional Practices and Methods of Assessment
New Emirates Medical Journal Secondary Stroke Prevention in Patients with Cryptogenic Stroke and Patent Foramen Ovale
Vascular Disease Prevention (Discontinued) Cardiovascular Diseases in Pregnancy - A Brief Overview
Current Cardiology Reviews Editorial (Thematic Issue: Cardiovascular Drug Therapy in Paediatric Age: From Metabolomics to Clinical Practice)
Current Medicinal Chemistry Serum Endocan, Neuron-Specific Enolase and Ischemia-Modified Albumin Levels in Newborns with Partial Blood Exchange Transfusion
Combinatorial Chemistry & High Throughput Screening