Salicylate, pharmacokinetics, and the pediatrician

PEDIATRICS ◽  
1974 ◽  
Vol 54 (6) ◽  
pp. 670-672
Author(s):  
Alan K. Done
Keyword(s):  
Clinical Pharmacology ◽  
Volume Of Distribution ◽  
Pediatric Drug ◽  
Legal Constraints ◽  
Drug Studies

Clinicians may, at first glance, wonder why the paper in this issue by Levy and Yaffe1 on the volume of distribution of salicylate in children should concern them or, indeed, why it even appears in their journal. This important and excellent study is a prime example of the growing influence and involvement of clinical pharmacology and pharmacokinetics in medicine generally and pediatrics particularly. Already substantial, with the growing complexity of pediatric therapeutics, this relationship stands to become even more widespread and intense as a result of increasing emphasis on more and better pediatric drug studies. Evolving ethical-legal constraints notwithstanding,2 these must and will expand.

scholarly journals Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Gian Maria Pacifici
Keyword(s):  
Clinical Pharmacology ◽  
Intranasal Administration ◽  
Rapid Onset ◽  
Volume Of Distribution ◽  
Multiple Organ ◽  
Onset Of Action ◽  
Antiepileptic Agent ◽  
Antiepileptic Therapy ◽  
Duration Of Effect ◽  
Ecmo Therapy

Midazolam is a benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults. Midazolam is hydroxylated by CYP3A4 and CYP3A5; the activities of these enzymes surge in the liver in the first weeks of life and thus the metabolic rate of midazolam is lower in neonates than in adults. Midazolam acts as a sedative, as an antiepileptic, for those infants who are refractory to standard antiepileptic therapy, and as an anaesthetic. Information of midazolam as an anaesthetic in infants are very little. Midazolam is usually administered intravenously; when minimal sedation is required, intranasal administration of midazolam is employed. Disease affects the pharmacokinetics of midazolam in neonates; multiple organ failure reduces the Cl of midazolam and mechanical ventilation prolongs thet1/2of this drug. ECMO therapy increasest1/2, Cl, and Vd of midazolam several times. The adverse effects of midazolam in neonates are scarce: pain, tenderness, and thrombophlebitis may occur. Respiratory depression and hypotension appear in a limited percentage of infants following intravenous infusion of midazolam. In conclusion, midazolam is a safe and effective drug which is employed as a sedative, as antiepileptic agent, for infants who are refractory to standard antiepileptic therapy, and as an anaesthetic.

scholarly journals The Revolution in Pediatric Drug Development and Drug Use: Therapeutic Orphans No More

2020 ◽  
Vol 25 (7) ◽  
pp. 565-573
Author(s):  
Gilbert J. Burckart ◽  
Clara Kim
Keyword(s):  
Drug Development ◽  
Pediatric Population ◽  
Scientific Evidence ◽  
Pediatric Drug ◽  
Drug Dosing ◽  
Pediatric Drug Development ◽  
Lack Of Information ◽  
Lifetime Achievement ◽  
Pediatric Pharmacology ◽  
Drug Studies

This lecture was given by Dr. Burckart in association with presentation of the 2014 Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics, which is selected by the Pediatric Pharmacy Association. Multiple factors make conducting drug studies in the pediatric population difficult, resulting in a historic lack of information surrounding safe and efficacious drug dosing in children. The paradigm in pediatric drug development has shifted from normal science being that children are therapeutic orphans in the drug development system, to a model drift caused by pediatric legislation, to a model crisis caused by failed pediatric drug development trials, to finally a model revolution that includes pediatric patients routinely in drug development. Major regulatory actions and the accumulation of scientific evidence has created an environment where clinicians can expect properly labeled drug usage information for the pediatric population.

scholarly journals Pharmacokinetics of the disialoganglioside, GD2, a circulating tumor biomarker for neuroblastoma, in nonhuman primates

2021 ◽  
Vol 10 ◽  
pp. 26-29
Author(s):  
Frank M. Balis ◽  
Cynthia Lester McCully ◽  
Christine M. Busch ◽  
Elizabeth Fox ◽  
Katherine E. Warren
Keyword(s):  
Clinical Pharmacology ◽  
Childhood Cancer ◽  
High Performance ◽  
Nonhuman Primates ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Tumor Biomarker ◽  
Ganglioside Gd2 ◽  
Reservoir Systems ◽  
Csf Pharmacokinetics

Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer, neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Methods: We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the C18 lipoform of GD2 in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems. GD2 was quantified with a validated high-performance liquid chromatography (HPLC)/tandem mass spectrometry assay. GD2 was administered as a short intravenous infusion and frequent plasma and CSF samples were drawn over 72 hours. Results: GD2 plasma concentration declined monoexponentially with a half-life of 16 hours. Clearance was 0.0136 and 0.0131 L/h and volume of distribution (Vd) was 0.035 and 0.038 L/kg in the two animals. Vd was equivalent to plasma volume. Greater than 98% of GD2 in plasma is in a bound form consistent with its known association with lipoproteins and accounting for its limited volume of distribution. GD2 did not cross over from plasma into the CSF. Conclusions: The pharmacokinetic profile of GD2 is favorable for a circulating tumor biomarker. This study demonstrates the value of characterizing the clinical pharmacology of circulating biomarkers to better understand their clinical behavior.

scholarly journals Promoting Appropriate Use of Drugs in Children

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Vijay N. Yewale ◽  
Dhanya Dharmapalan
Keyword(s):  
Drug Resistance ◽  
Adverse Effects ◽  
Significant Variation ◽  
Pediatric Population ◽  
Causative Organism ◽  
Drug Trials ◽  
Appropriate Use ◽  
Pediatric Drug ◽  
Off Label ◽  
Drug Studies

Promotion of appropriate and safe drugs in children is the need of the hour globally. Pediatric population by itself is a spectrum of different physiologies with significant variation in pharmacodynamics and pharmacokinetics. Unfortunately, 50–90% of drugs used in children today have never been actually studied in this population, and the results of drug studies done in adults are often extrapolated for use in children. Many medicines in pediatrics are off label or unlicensed. There is a spurt in drug resistance due to the overzealous prescription of antimicrobials not indicated, such as, using inadequate dosage or duration of drug regime leading to partially treated infections, using the wrong antimicrobial due to ignorance of causative organism, and finally using indigenous, irrational combinations. Availability of properly labeled and safe pediatric formulations, regular audit by pharmacists, judicious prescriptions, proper counseling about drug administration, surveillance of adverse effects, and pediatric drug trials can be the best possible interventions to offer appropriate medicines to children and thereby save millions of lives.

scholarly journals The Infancy of an International Paediatric Pharmacy Network

2008 ◽  
Vol 13 (1) ◽  
pp. 51-54
Author(s):  
David Knoppert ◽  
Sara Arenas-Lopez ◽  
Rowena McArtney
Keyword(s):  
Clinical Pharmacology ◽  
Drug Therapy ◽  
Interest Groups ◽  
Special Interest ◽  
Special Interest Groups ◽  
Pediatric Drug ◽  
International Network

There are several pharmacy and clinical pharmacology organizations in which pediatrics is one of many special interest groups and a few whose focus is entirely pediatric drug therapy. Recently the foundation for the establishment of an International Network of Paediatric Pharmacists has been laid. This paper describes that network.

Clinical Pharmacology of Local Anaesthetics

Anaesthesia ◽  
2000 ◽  
Vol 55 (9) ◽  
pp. 938-938
Author(s):  
K. R. Milligan
Keyword(s):  
Clinical Pharmacology ◽  
Local Anaesthetics
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