British journal of clinical pharmacology
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Br J Clin Pharmacol · Mar 2015
ReviewImproving antibiotic prescribing for children in the resource-poor setting.
Antibiotics are a critically important part of paediatric medical care in low- and middle-income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. ⋯ The World Health Organization initiatives, such as 'Make medicines child size', the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence-based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing.
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Br J Clin Pharmacol · Mar 2015
Randomized Controlled TrialMetabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1.
The rare association of flupirtine with liver injury is most likely caused by reactive quinone diimines and their oxidative formation may be influenced by the activities of N-acetyltransferases (NAT) that conjugate the less toxic metabolite D13223, and by glucuronosyltransferases (UGT) and glutathione S-transferases (GST) that generate stable terminal glucuronides and mercapturic acid derivatives, respectively. The influence of genetic polymorphisms of NAT2, UGT1A1 and GSTP1 on generation of the terminal mercapturic acid derivatives and analgesic effects was evaluated to identify potential genetic risk factors for hepatotoxicity of flupirtine. ⋯ Formation of mercapturic acid derivatives is a major elimination route for flupirtine in man. However, the theoretically toxic pathway is not influenced by the frequent polymorphisms of UGT1A1, NAT2 and GSTP1.