Subject(s)
Biomedical Research , Health Services Research , Biomedical Research/ethics , Biomedical Research/organization & administration , Child , Child Welfare , Ethics, Research , Health Services Research/ethics , Health Services Research/organization & administration , Humans , Quality Improvement , United KingdomABSTRACT
Having some understanding of pharmacokinetics is important for all clinicians when prescribing medications. Key elements to effective and safe prescribing include making sure that we don't underdose a medication making it ineffective, but also do not overprescribe a treatment known to cause toxic effects. In paediatrics, there are significant physiological and developmental differences that add to the challenges of safe prescribing. This article aims to provide the clinician with some basic paediatric pharmacokinetic principles with clinical examples to aid their prescribing skills.
Subject(s)
Pharmacokinetics , Biological Availability , Child , Half-Life , Humans , Metabolic Clearance Rate , Tissue DistributionABSTRACT
Intravenous salbutamol is commonly used to treat children with severe asthma unresponsive to inhaled ß2-agonist therapy. However, in this setting, there is little clinical trial data demonstrating its effectiveness. Additionally, there are significant concerns that intravenous salbutamol-dosing recommendations for children with acute asthma are excessive, and unnecessarily raise the potential for adverse reactions, such as lactic acidosis and tachycardia which, by increasing respiratory workload, exacerbate respiratory failure. Here, we review salbutamol clinical pharmacology and toxicology, evidence relating to its use in acute asthma and highlight gaps in the evidence base.
Subject(s)
Adrenergic beta-2 Receptor Agonists/therapeutic use , Albuterol/therapeutic use , Asthma/drug therapy , Acute Disease , Adrenergic beta-2 Receptor Agonists/adverse effects , Albuterol/adverse effects , Child , Child, Preschool , Evidence-Based Medicine , Humans , Infusions, Intravenous , Treatment OutcomeSubject(s)
Anesthesia, General/statistics & numerical data , Conscious Sedation/statistics & numerical data , Child , Child, Preschool , England , Hospitals, Teaching/statistics & numerical data , Humans , Infant , Magnetic Resonance Imaging/methods , Professional Practice/statistics & numerical dataSubject(s)
Conscious Sedation , Hypnotics and Sedatives/administration & dosage , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Child , Chloral Hydrate/metabolism , Chloral Hydrate/pharmacology , Conscious Sedation/methods , Dexmedetomidine/administration & dosage , Humans , Hypnotics and Sedatives/metabolism , Hypnotics and Sedatives/pharmacology , Intestinal Absorption , Ketamine/administration & dosage , Midazolam/administration & dosage , Pentobarbital/administration & dosage , Propofol/administration & dosage , Temazepam/administration & dosage , Thiopental/administration & dosageABSTRACT
AIM: The safety of clinical trials in children has not been previously studied. We aimed to identify how safety is monitored and the extent of adverse drug reactions (ADRs). METHODS: A literature review of the Medline Database for therapeutic clinical trials involving oral and intravenous medicines in children from 1996 to 2002. Papers were read to determine the safety monitoring and the presence of adverse events (AEs) or ADRs. RESULTS: Seven hundred thirty-nine trials were identified. Thirteen (2%) had safety monitoring committees (SMCs). Five hundred twenty-three (71%) trials reported AEs and 151 (20%) of these trials reported a serious AE. ADRs were present in 270 (36.5%) trials, with 80 (11%) of trials having a moderate or severe ADR. Six clinical trials were terminated early because of significant drug toxicity. All of these had SMCs. There were deaths in 83 (11%) trials. In the majority of trials, mortality was thought to be unrelated to the investigational drug; however, in two trials mortality was higher in the treatment group. CONCLUSIONS: About 11% of trials have a moderate or severe ADR. All paediatric clinical trials should have a SMC.
Subject(s)
Clinical Trials Data Monitoring Committees , Clinical Trials as Topic/statistics & numerical data , Child , Clinical Trials as Topic/adverse effects , Drug-Related Side Effects and Adverse Reactions , Humans , Pediatrics/standards , SafetyABSTRACT
BACKGROUND: Ethical problems are quoted as a reason not to perform clinical trials in children. Little is known about the views of researchers regarding ethics. OBJECTIVES: A pilot study was conducted to assess the applicability of a questionnaire design containing trial scenarios to examine views regarding the use of children in drug trials and to elicit possible international differences. SETTING: Paediatricians and researchers in the United Kingdom and Canada. METHODS: Responders were presented with a questionnaire containing direct questions and six trial scenarios, each containing an ethical dilemma. Responders were asked regarding their own approval and their perceived opinion of whether an ethical review board (ERB) would approve. RESULTS: One hundred questionnaires (50 each country) were received. Few responders had research ethics training (14% United Kingdom and 8% Canada). Most (80 and 88%) felt children could be harmed by participation in trials and half (47 and 59%) felt children should only participate if they receive direct benefit. Many (58 and 61%) disagreed with payments beyond travel expenses. In the trial scenarios, 34% of responders were willing to enter healthy children in a pharmacokinetics study of an antibiotic for cystic fibrosis and 22% considered their ERBs would approve. Only a third (33%) would enter children in an analgesia trial that was placebo-controlled. CONCLUSION: Using healthy children and placebos in trials caused concern. Similar views were found between the two countries. The majority had no training in research ethics. The study highlights the usefulness of a questionnaire with clinical trial scenarios to try to elicit views on the ethics of conducting research in children.
