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Optimising Formulations for Paediatric Patients with Inherited Metabolic Disorders: The Case Study of Levocarnitine

Stephen Tomlin1, Chris Mühlhausen2, Andriy Krendyukov3

  • 1Director Children's Medicines Research and Innovation Centre, Great Ormond Street Hospital for Children, London, WC1N 1EP, UK.

Pharmaceutical Medicine
|June 4, 2026
PubMed

Insights

Drug excipients pose risks for infants with inherited metabolic disorders (IMDs). Safer, transparent formulations are crucial for neonates requiring long-term treatment to prevent toxicity and improve outcomes.

Area of Science:

  • Pharmacology and Toxicology
  • Paediatric Medicine
  • Genetics and Rare Diseases

Background:

  • Inherited metabolic disorders (IMDs) disrupt biochemical pathways, necessitating careful pharmacological management.
  • Infants and neonates have unique physiological challenges, including immature organ systems and altered metabolism, increasing sensitivity to drug excipients.
  • Lifelong treatments for conditions like primary carnitine deficiency (PCD) highlight the importance of excipient safety in paediatric drug formulations.

Purpose of the Study:

  • To highlight the challenges of drug excipient selection in paediatric pharmacological management for inherited metabolic disorders.
  • To underscore the potential risks of common excipients in vulnerable neonates and infants with IMDs.
  • To advocate for improved regulatory frameworks, formulation transparency, and interdisciplinary collaboration for safer paediatric drug treatments.

Main Methods:

  • Review of current regulatory guidelines and databases (e.g., STEP, SEEN) for paediatric excipient safety data.
  • Analysis of challenges in excipient transparency, standardization, and labelling in paediatric drug formulations.
  • Discussion of clinical decision-making complexities due to lack of precise excipient concentration data.

Main Results:

  • Common excipients (e.g., parabens, benzoates, propylene glycol) may pose risks to neonates with IMDs due to immature metabolism.
  • Existing regulatory frameworks are evolving but significant gaps in excipient transparency and standardization persist.
  • Healthcare providers face difficulties in assessing cumulative excipient exposure, especially in polypharmacy scenarios.

Conclusions:

  • There is a critical need for age-appropriate, excipient-conscious drug formulations for children with IMDs, particularly neonates.
  • Enhanced regulatory oversight and increased formulation transparency are essential to minimize risks associated with drug excipients.
  • Interdisciplinary collaboration is vital to improve the safety and efficacy of paediatric treatments for rare metabolic disorders.

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