Downregulation of Hepatic Carbonyl Reductase Type 1 in End-Stage Renal Disease
The functional expression of several hepatic drug metabolizing enzymes and transporters are altered in patients with end-stage renal disease (ESRD). We aimed to assess the effect of ESRD on the expression and function of hepatic reductases. Cytosolic and microsomal fractions were isolated from liver tissue from deceased ESRD (n=10) and deceased control patients (n=11). Gene and protein expression, and metabolic activity of reductases were assessed by conducting qRT-PCR, Western blotting and enzyme kinetics, respectively. A 65% decrease in carbonyl reductase 1 protein expression (p (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Adverse Drug Events in Children: How Big is the Problem?
Adverse drug events in children is an under appreciated but significant cause of health care contact resulting in ED visits and hospital admissions with associated resource utilization. In recent years we have started to better understand the impact of ADEs in children but there remains significant questions that must be addressed to further improve our understanding of the etiology of these ADEs and strategies for prevention and management. This paper will describe what is known regarding the frequency, severity, preventability and classification of ADEs in children. It will also describe some of the challenges and unansw...
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Ontogeny of Human Conjugating Enzymes
Understanding the detailed ontogeny of xenobiotic metabolizing enzymes is important if we are to be able to predict the risk of toxicity to the developing fetus or the fate of drugs in neonates and children. This review summarizes current knowledge of the development of the major families of conjugating enzymes in humans: the UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, arylamine N-acetyltransferases and methyltransferases; little is known of the last three. Based on the available information, sulfation appears to be the most highly developed pathway during fetal development where glucuronid...
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
The Effects of Obesity on Drug Metabolism in Children
Obesity in children is a significant clinical concern. There are many anecdotes and case studies regarding specific reactions of obese children to medications including therapeutic failure, adverse drug reactions and/or requirements for higher weight-adjusted dosing. There isis, however, a lack of basic and clinical data dissecting the mechanisms of these effects on pharmaceutical efficacy and safety. At present it is unknown how much of the difference in drug disposition in obese children can be attributed to obesity, to maturation or to an interaction between the two. Since a major determinant of drug disposition is hepa...
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Predicting Pediatric Drug Disposition-Present and Future Directions of Pediatric Physiologically-Based Pharmacokinetics
This mini-review examines the current state of pediatric physiologically-based pharmacokinetic (PBPK) modeling, including methodologies, approaches, and recent developments. Also discussed are United States regulations that have helped to shape the pediatric PBPK landscape and the ongoing urgent need for pediatric clinical studies. Finally, current pediatric PBPK software as well as the areas of focus for future studies will be reviewed. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Alterations in Hepatic Lipid Metabolism, and their Relation to Dietary Macronutrients in Pediatric Nonalcoholic Fatty Liver Disease
Nonacoholic fatty liver disease (NAFLD) is a common complication of pediatric obesity in which diet is a major factor in causation and the cornerstone of treatment. In this review, the alterations in hepatic lipid metabolism that contribute to pediatric NAFLD, and impact of dietary proteins, carbohydrates, and fats on hepatic fat metabolism and NAFLD are described. Lastly, dietary recommendations for achieving changes in macronutrient intakes that can be beneficial in the treatment of NAFLD are provided. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Biochemical Screening for in utero Drug Exposure
Licit and illicit drug use is a common complication of pregnancy. Accurate information on drug use is difficult to obtain for many reasons as women fear self-disclosure or consenting for drug testing due to stigma, guilt, and fear of social and legal harm. As information about drug use is clinically very important, biochemical testing is an important adjunct to careful maternal history. In addition, research studies depend on accurate measures of exposure when reporting risks of a substance. This paper delineates available matrices for and methods of biochemical drug testing in pregnant women and neonates. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Editorial (Thematic Issue: Recent Advances in Developmental Drug Disposition)
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
Meet Our Editorial Board Member:
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 18, 2015 Category: Drugs & Pharmacology Source Type: research
