Discontinuities and disruptions in drug dosage guidelines for the paediatric population

Historically, instead of conducting well-designed research studies in the pediatric population, drug monographs indicate that safety and efficacy in children have not been evaluated. Among the main challenges in clinical trials for children, ethical issues occupy a special place, as they arise at almost all stages — from clinical trials to extrapolation. In the article, the authors present the history of clinical research in pediatrics and neonatology, how the view of involving children in clinical trials has changed, the specific ethical problems of children’s participation in clinical trials, legislative initiatives and other agreed measures taken and what they have led to. The ethical issues of microdosing in pediatrics, methods for the first-in-pediatric dose selection, issues of acceptability and drug development for the treatment of rare diseases are discussed separately. Conducting trials in the most vulnerable pediatric groups — newborns and premature newborns — is presented in detail. The potential reasons for trial failures in children are presented with specific examples.

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Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration

Singu,

Verbeeck,

Pieper

et al. 2024

Children

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(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates. A dose of 5 mg/kg gentamicin was administered over 3–5 s every 24 h in combination with benzylpenicillin 100,000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Two blood samples were collected from each participant using a truncated pharmacokinetic sampling schedule. (3) Results: The one-compartment linear pharmacokinetic model best described the data. Birthweight, postnatal age, and white blood cell count were predictive of clearance (CL), while birthweight was predictive of volume (V). For the typical neonate (median weight 1.57 kg, median postnatal age 4 days (0.011 years), median log-transformed WBC of 2.39), predicted CL and V were 0.069 L/h and 0.417 L, respectively—similar to literature values. Simulated gentamicin concentrations varied with respect to postnatal age and bodyweight. (4) Conclusions: A 5 mg/kg/24 h dosage regimen yielded simulated gentamicin concentrations with respect to age and birthweight similar to those previously reported in the literature to be safe and efficacious, confirming its appropriateness.

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Discontinuities and disruptions in drug dosage guidelines for the paediatric population

Cited by 3 publications

References 29 publications

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Population pharmacokinetics of methotrexate in paediatric patients with acute lymphoblastic leukaemia and malignant lymphoma

Ethical issues in pediatric clinical trials

Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration

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