Pediatric Drugs

, Volume 18, Issue 3, pp 231–233 | Cite as

Substitution as a Strategy to Improve Excipient Exposure in Neonates: One Piece of the Puzzle

  • Karel Allegaert
  • Isabel Spriet


Since extensive variability is the key characteristic of neonatal pharmacology despite an overall low elimination capacity, this should translate in drug formulations to low, adjustable and flexible dosing to maintain dose accuracy. This observation is not limited to the active compounds, but also applies to excipients [1, 2].

In this issue of the journal, Nellis et al. quantified the potential impact of systematic product substitution within Europe as a strategy to reduce exposure to potentially harmful excipients (i.e. parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol and ethanol) in neonates [3]. The authors hereby explored the between-country variability in exposure to excipients in formulations administered to 726 neonates in 21 different European countries. Using availability of the same active pharmaceutical ingredient with a similar dosage form (but not similar strength/concentration) as prerequisites, substitution potentially...


Propylene Glycol Poloxamer Systematic Strategy Flexible Dose Saccharin Sodium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The clinical research of K Allegaert was supported by the Fund for Scientific Research, Flanders (fundamental clinical investigatorship 1800214N) and the research activities are further facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033).

Compliance with Ethical Standards

Conflict of interest

K. Allegaert and I. Spriet declare that they have no relevant conflicts of interest.

Source of funding

No sources of funding were used to support the writing of this manuscript.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Intensive Care and Department of SurgeryErasmus MC-Sophia Children’s HospitalRotterdamThe Netherlands
  2. 2.Department of Development and RegenerationKU LeuvenLeuvenBelgium
  3. 3.Pharmacy DepartmentUniversity Hospitals LeuvenLeuvenBelgium
  4. 4.Department of Pharmacological and Pharmaceutical SciencesClinical Pharmacology and Pharmacotherapy, KU LeuvenLeuvenBelgium
  5. 5.Neonatal Intensive Care UnitUniversity HospitalLeuvenBelgium

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