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Have we neglected to study target-site drug exposure in children? A systematic review of the literature

Eline Hermans (UGent) , Jozefien Meersschaut (UGent) , Isis Van herteryck (UGent) , Mathias Devreese (UGent) , Johan Vande Walle (UGent) , Peter De Paepe (UGent) and Pieter De Cock (UGent)
(2024) CLINICAL PHARMACOKINETICS. 63(4). p.439-468
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Abstract
Background and ObjectiveDrug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population.MethodsA systematic literature search was performed in the MEDLINE and Embase databases.ResultsForty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1-93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited.ConclusionThe influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.
Keywords
Pharmacology (medical), Pharmacology, microdialysis, tissue pharmacokinetics

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MLA
Hermans, Eline, et al. “Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature.” CLINICAL PHARMACOKINETICS, vol. 63, no. 4, 2024, pp. 439–68, doi:10.1007/s40262-024-01364-5.
APA
Hermans, E., Meersschaut, J., Van herteryck, I., Devreese, M., Vande Walle, J., De Paepe, P., & De Cock, P. (2024). Have we neglected to study target-site drug exposure in children? A systematic review of the literature. CLINICAL PHARMACOKINETICS, 63(4), 439–468. https://doi.org/10.1007/s40262-024-01364-5
Chicago author-date
Hermans, Eline, Jozefien Meersschaut, Isis Van herteryck, Mathias Devreese, Johan Vande Walle, Peter De Paepe, and Pieter De Cock. 2024. “Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature.” CLINICAL PHARMACOKINETICS 63 (4): 439–68. https://doi.org/10.1007/s40262-024-01364-5.
Chicago author-date (all authors)
Hermans, Eline, Jozefien Meersschaut, Isis Van herteryck, Mathias Devreese, Johan Vande Walle, Peter De Paepe, and Pieter De Cock. 2024. “Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature.” CLINICAL PHARMACOKINETICS 63 (4): 439–468. doi:10.1007/s40262-024-01364-5.
Vancouver
1.
Hermans E, Meersschaut J, Van herteryck I, Devreese M, Vande Walle J, De Paepe P, et al. Have we neglected to study target-site drug exposure in children? A systematic review of the literature. CLINICAL PHARMACOKINETICS. 2024;63(4):439–68.
IEEE
[1]
E. Hermans et al., “Have we neglected to study target-site drug exposure in children? A systematic review of the literature,” CLINICAL PHARMACOKINETICS, vol. 63, no. 4, pp. 439–468, 2024.
@article{01HW5X47WT5YKCCPWMF6N8ATX9,
  abstract     = {{Background and ObjectiveDrug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population.MethodsA systematic literature search was performed in the MEDLINE and Embase databases.ResultsForty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1-93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited.ConclusionThe influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.}},
  author       = {{Hermans, Eline and Meersschaut, Jozefien and Van herteryck, Isis and Devreese, Mathias and Vande Walle, Johan and De Paepe, Peter and De Cock, Pieter}},
  issn         = {{0312-5963}},
  journal      = {{CLINICAL PHARMACOKINETICS}},
  keywords     = {{Pharmacology (medical),Pharmacology,microdialysis,tissue pharmacokinetics}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{439--468}},
  title        = {{Have we neglected to study target-site drug exposure in children? A systematic review of the literature}},
  url          = {{http://doi.org/10.1007/s40262-024-01364-5}},
  volume       = {{63}},
  year         = {{2024}},
}

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