Skip to content
2000
image of The Current and Potential Role of Pediatric Clinical Pharmacologists in Italy: A Review with Evidence Synthesis and Literature Analysis

Abstract

Background

Considering infants and young children, it is well established that their physiological and developmental peculiarities should not be confused with those of other patient categories, such as adults or vulnerable patients. Indeed, their anatomic-functional characteristics specifically influence the drug pharmacokinetic/pharmacodynamic profile. Therefore, the availability of specialists devoted to pediatric pharmacology within multidisciplinary teams is highly desirable to improve the care of these patients.

Objective

This work aims to describe the role of pediatric clinical pharmacologists in the context of pediatric clinical care in Italy, using a qualitative method based on the type of articles published.

Methods

A literature review was conducted according to the PRISMA guidelines, considering articles published on the PubMed database between January 2017 and March 2022 and using specific MeSH terms. The papers were attributed to two blind assessors and then processed for discussion. To support article screening, focusing on the words contained in article titles, the R package evidence synthesis tool was used.

Results

The search identified a total of 1544 articles, of which 93 were selected. The articles analyzed mainly concern therapeutic drug monitoring and pharmacovigilance with adverse drug reactions.

Conclusion

An insight into multidisciplinary work to prevent, diagnose, and treat pediatric diseases and to monitor treatments is provided in this study. However, this concept needs to be strengthened in the long term.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673291434250612050205
2025-07-01
2025-09-10

  • From This Site

    /content/journals/cmc/10.2174/0109298673291434250612050205
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Kearns G.L. Abdel-Rahman S.M. Alander S.W. Blowey D.L. Leeder J.S. Kauffman R.E. Developmental pharmacology-drug disposition, action, and therapy in infants and children. N. Engl. J. Med. 2003 349 12 1157 1167 10.1056/NEJMra035092 13679531
    [Google Scholar]
  2. Guidi B. Parziale A. Nocco L. Maiese A. Russa L.R. Paolo D.M. Turillazzi E. Regulating pediatric off-label uses of medicines in the EU and USA: Challenges and potential solutions. Int. J. Clin. Pharm. 2022 44 1 264 269 10.1007/s11096‑021‑01303‑5 34495453
    [Google Scholar]
  3. van der Zanden T.M. Smeets N.J.L. Hoop-Sommen D.M. Schwerzel M.F.T. Huang H.J. Barten L.J.C. van der Heijden J.E.M. Freriksen J.J.M. Horstink A.A.L. Holsappel I.H.G. Mooij M.G. Hoog D.M. Wildt D.S.N. Off-label, but on-evidence? a review of the level of evidence for pediatric pharmacotherapy. Clin. Pharmacol. Ther. 2022 112 6 1243 1253 10.1002/cpt.2736 36069288
    [Google Scholar]
  4. Rose K. Grant-Kels J.M. Striano P. Therapeutic orphans, off-label, pediatric drug development: Towards reasonable pharmacotherapy for minors. Expert Opin. Pharmacother. 2024 25 18 2375 2384 10.1080/14656566.2024.2426678 39526437
    [Google Scholar]
  5. Turner M.A. Hildebrand H. Fernandes R.M. Wildt D.S.N. Mahler F. Hankard R. Leary R. Bonifazi F. Nobels P. Cheng K. Attar S. Rossi P. Rocchi F. Claverol J. Nafria B. Giaquinto C. The conect4children (c4c) consortium: Potential for improving european clinical research into medicines for children. Pharmaceut. Med. 2021 35 2 71 79 10.1007/s40290‑020‑00373‑6 33539007
    [Google Scholar]
  6. Goulooze SC Vis PW Krekels EHJ Knibbe CAJ. Advances in pharmacokinetic-pharmacodynamic modelling for pediatric drug development: Extrapolations and exposure-response analyses. Expert Rev. Clin. Pharmacol. 2023 16 12 1201 1209 10.1080/17512433.2023.2288171
    [Google Scholar]
  7. Durairaj C. Bhattacharya I. Challenges, approaches and enablers: Effectively triangulating towards dose selection in pediatric rare diseases. J. Pharmacokinet. Pharmacodyn. 2023 50 6 445 459 10.1007/s10928‑023‑09868‑6 37296230
    [Google Scholar]
  8. Kuzma N. Kersten H.B. Thompson E.D. Evidence-based medicine in the clinical learning environment of pediatric hospital medicine. Pediatr. Clin. North Am. 2019 66 4 713 724 10.1016/j.pcl.2019.03.001 31230618
    [Google Scholar]
  9. Randell R.L. Gelineau-Morel R. Thomas S. Gonzalez D. Leeder J.S. Hornik C.P. Training the next generation of pediatric clinical pharmacologists: Insights and trainee perspectives over 10 years. J. Clin. Pharmacol. 2024 65 3 389 395 10.1002/jcph.6155 39535328
    [Google Scholar]
  10. Walsh J. Schaufelberger D. Iurian S. Klein S. Batchelor H. Turner R. Gizurarson S. Boltri L. Alessandrini E. Tuleu C. Path towards efficient paediatric formulation development based on partnering with clinical pharmacologists and clinicians, a conect 4 children expert group white paper. Br. J. Clin. Pharmacol. 2022 88 12 5034 5051 10.1111/bcp.14989 34265091
    [Google Scholar]
  11. Moher D. Liberati A. Tetzlaff J. Altman D.G. PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009 6 7 e1000097 10.1371/journal.pmed.1000097 19621072
    [Google Scholar]
  12. Westgate M.J. revtools: An R package to support article screening for evidence synthesis. Res. Synth. Methods 2019 10 4 606 614 10.1002/jrsm.1374 31355546
    [Google Scholar]
  13. Carello R. Ricottini L. Miranda V. Panei P. Rocchi L. Arcieri R. Galli E. Long-term treatment with low- dose medicine in chronic childhood eczema: A double-blind two-stage randomized control trial. Ital. J. Pediatr. 2017 43 1 78 10.1186/s13052‑017‑0393‑5 28874171
    [Google Scholar]
  14. Leroux S. Jacqz-Aigrain E. Elie V. Legrand F. Barin-Le Guellec C. Aurich B. Biran V. Dusang B. Goudjil S. Coopman S. Sanchez G.R. Zhao W. Manzoni P. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: A randomized, open-label clinical trial. Br. J. Clin. Pharmacol. 2018 84 9 1989 1999 10.1111/bcp.13628 29744900
    [Google Scholar]
  15. Filippi L. Cavallaro G. Bagnoli P. Monte D.M. Fiorini P. Berti E. Padrini L. Donzelli G. Araimo G. Cristofori G. Fumagalli M. Marca L.G. Bona D.M.L. Pasqualetti R. Fortunato P. Osnaghi S. Tomasini B. Vanni M. Calvani A.M. Milani S. Cortinovis I. Pugi A. Agosti M. Mosca F. Propranolol 0.1% eye micro- drops in newborns with retinopathy of prematurity: A pilot clinical trial. Pediatr. Res. 2017 81 2 307 314 10.1038/pr.2016.230 27814346
    [Google Scholar]
  16. Filippi L. Cavallaro G. Berti E. Padrini L. Araimo G. Regiroli G. Raffaeli G. Bozzetti V. Tagliabue P. Tomasini B. Mori A. Buonocore G. Agosti M. Bossi A. Chirico G. Aversa S. Fortunato P. Osnaghi S. Cavallotti B. Suzani M. Vanni M. Borsari G. Donati S. Nascimbeni G. Nardo D. Piermarocchi S. Marca L.G. Forni G. Milani S. Cortinovis I. Calvani M. Bagnoli P. Monte D.M. Calvani A.M. Pugi A. Villamor E. Donzelli G. Mosca F. Propranolol 0.2% eye micro-drops for retinopathy of prematurity: A prospective phase IIB study. Front Pediatr. 2019 7 180 10.3389/fped.2019.00180 31134171
    [Google Scholar]
  17. Mancuso M.E. Mahlangu J. Sidonio R. Jr Trask P. Uguen M. Chang T. Shima M. Young G. Oldenburg J. Mackensen V.S. Health-related quality of life and caregiver burden of emicizumab in children with haemophilia A and factor VIII inhibitors—Results from the HAVEN 2 study. Haemophilia 2020 26 6 1009 1018 10.1111/hae.14183 33084175
    [Google Scholar]
  18. Nobili V. Alisi A. Mosca A. Crudele A. Zaffina S. Denaro M. Smeriglio A. Trombetta D. The antioxidant effects of hydroxytyrosol and vitamin e on pediatric nonalcoholic fatty liver disease, in a clinical trial: A new treatment? Antioxid. Redox Signal. 2019 31 2 127 133 10.1089/ars.2018.7704 30588836
    [Google Scholar]
  19. Esposito C. Conte D.F. Cerulo M. Coppola V. Esposito G. Ricciardi E. Crocetto F. Castagnetti M. Calignano A. Escolino M. Evaluation of efficacy of oxygen-enriched oil-based gel dressing in patients who underwent surgical repair of distal hypospadias: A prospective randomised clinical trial. World J. Urol. 2021 39 6 2205 2215 10.1007/s00345‑020‑03419‑1 32852619
    [Google Scholar]
  20. Ciccia M. Chakrokh R. Molinazzi D. Zanni A. Farruggia P. Sandri F. Skin antisepsis with 0.05% sodium hypochlorite before central venous catheter insertion in neonates: A 2-year single-center experience. Am. J. Infect. Control 2018 46 2 169 172 10.1016/j.ajic.2017.08.012 28967509
    [Google Scholar]
  21. Pane M. Palermo C. Messina S. Sansone V.A. Bruno C. Catteruccia M. Sframeli M. Albamonte E. Pedemonte M. D’Amico A. Brigati G. Sanctis D.R. Coratti G. Lucibello S. Bertini E. Vita G. Tiziano F.D. Mercuri E. Nusinersen in type 1 SMA infants, children and young adults: Preliminary results on motor function. Neuromuscul. Disord. 2018 28 7 582 585 10.1016/j.nmd.2018.05.010 29960818
    [Google Scholar]
  22. Jóźwiak S. Veggiotti P. Moreira J. Gama H. Rocha F. Soares-da-Silva P. Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures. Epilepsy Behav. 2018 81 1 11 10.1016/j.yebeh.2018.01.029 29454255
    [Google Scholar]
  23. Falsaperla R. Mauceri L. Pavone P. Barbagallo M. Vitaliti G. Ruggieri M. Pisani F. Corsello G. Short-term neurodevelopmental outcome in term neonates treated with phenobarbital versus levetiracetam: A single-center experience. Behav. Neurol. 2019 2019 1 8 10.1155/2019/3683548 31281546
    [Google Scholar]
  24. Gatti M. Cojutti P.G. Campoli C. Caramelli F. Corvaglia L.T. Lanari M. Pession A. Ramirez S. Viale P. Pea F. A proof of concept of the role of TDM-based clinical pharmacological advices in optimizing antimicrobial therapy on real-time in different paediatric settings. Front. Pharmacol. 2021 12 755075 10.3389/fphar.2021.755075 34646143
    [Google Scholar]
  25. Girmenia C. Annino L. Bertaina A. Mariotti B. Caselli D. Fanci R. Barberi W. Marchesi F. Carotti A. Ferrari A. Cerchiara E. Cupelli L. Arcioni F. Ribersani M. Proia A. Cartoni C. Girardi K. Venditti A. Cassetta M.I. Fallani S. Novelli A. Voriconazole treatment in adults and children with hematological diseases: Can it be used without measurement of plasma concentration? Med. Mycol. 2018 56 3 263 278 10.1093/mmy/myx053 28992093
    [Google Scholar]
  26. Carlone G. Simeone R. Baraldo M. Maestro A. Zanon D. Barbi E. Maximova N. Area-under-the-curve-based mycophenolate mofetil dosage may contribute to decrease the incidence of graft-versus-host disease after allogeneic hematopoietic cell transplantation in pediatric patients. J. Clin. Med. 2021 10 3 406 10.3390/jcm10030406 33494356
    [Google Scholar]
  27. Nicolò D.A. Pinon M. Palermiti A. Nonnato A. Manca A. Mula J. Catalano S. Tandoi F. Romagnoli R. D’Avolio A. Calvo P.L. Monitoring tacrolimus concentrations in whole blood and peripheral blood mononuclear cells: Inter- and intra-patient variability in a cohort of pediatric patients. Front. Pharmacol. 2021 12 750433 10.3389/fphar.2021.750433 34803692
    [Google Scholar]
  28. Rizzari C. Lanvers-Kaminsky C. Valsecchi M.G. Ballerini A. Matteo C. Gerss J. Wuerthwein G. Silvestri D. Colombini A. Conter V. Biondi A. Schrappe M. Moericke A. Zimmermann M. Stackelberg V.A. Linderkamp C. Frühwald M.C. Legien S. Attarbaschi A. Reismüller B. Kasper D. Smisek P. Stary J. Vinti L. Barisone E. Parasole R. Micalizzi C. Zucchetti M. Boos J. Asparagine levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia treated with pegylated-asparaginase in the induction phase of the AIEOP-BFM ALL 2009 study. Haematologica 2019 104 9 1812 1821 10.3324/haematol.2018.206433 30705097
    [Google Scholar]
  29. Nasso C. Mecchio A. Rottura M. Valenzise M. Menniti-Ippolito F. Cutroneo P.M. Squadrito V. Squadrito F. Pallio G. Irrera N. Arcoraci V. Altavilla D. A 7-years active pharmacovigilance study of adverse drug reactions causing children admission to a pediatric emergency department in sicily. Front. Pharmacol. 2020 11 1090 10.3389/fphar.2020.01090 32765282
    [Google Scholar]
  30. Franco V. Barbieri M.A. Cutroneo P.M. Arena I. Cicala G. Marchione P. Spina E. Perucca E. Pediatric adverse reactions to antiseizure medications – An analysis of data from the Italian spontaneous reporting system (2001–2019). Epilepsy Behav. 2021 119 107989 10.1016/j.yebeh.2021.107989 33946010
    [Google Scholar]
  31. Pozzi M. Carnovale C. Mazhar F. Peeters G.G.A.M. Gentili M. Nobile M. Radice S. Clementi E. Adverse drug reactions related to mood and emotion in pediatric patients treated for attention deficit/hyperactivity disorder. J. Clin. Psychopharmacol. 2019 39 4 386 392 10.1097/JCP.0000000000001058 31205193
    [Google Scholar]
  32. Pietro D.P. Della Casa Alberighi O. Silvestri M. Tosca M.A. Ruocco A. Conforti G. Rossi G.A. Castagnola E. Merlano M.C. Zappettini S. Renna S. Monitoring adherence to guidelines of antibiotic use in pediatric pneumonia: The MAREA study. Ital. J. Pediatr. 2017 43 1 113 10.1186/s13052‑017‑0432‑2 29273072
    [Google Scholar]
  33. Lombardi N. Crescioli G. Bettiol A. Tuccori M. Rossi M. Bonaiuti R. Ravaldi C. Levi M. Mugelli A. Ricci S. Lippi F. Azzari C. Bonanni P. Vannacci A. Vaccines safety in children and in general population: A pharmacovigilance study on adverse events following anti-infective vaccination in italy. Front. Pharmacol. 2019 10 948 10.3389/fphar.2019.00948 31543816
    [Google Scholar]
  34. Carnovale C. Mahzar F. Scibelli S. Gentili M. Arzenton E. Moretti U. Leoni O. Pozzi M. Peeters G.G.A.M. Clementi E. Medaglia M. Radice S. Central nervous system-active drug abused and overdose in children: A worldwide exploratory study using the WHO pharmacovigilance database. Eur. J. Pediatr. 2019 178 2 161 172 10.1007/s00431‑018‑3281‑0 30374752
    [Google Scholar]
  35. Kaguelidou F. Holstiege J. Schink T. Bezemer I. Poluzzi E. Mazzaglia G. Pedersen L. Sturkenboom M. Trifirò G. ‘Use of antipsychotics in children and adolescents: A picture from the ARITMO population-based European cohort study’. Epidemiol. Psychiatr. Sci. 2020 29 e117 10.1017/S2045796020000293 32308179
    [Google Scholar]
  36. Regulation (EC) No 1901/2006 of the european parliament and of the council . 2006 Available from: http://data.europa.eu/eli/reg/2006/1901/oj/eng
  37. Regulation (EC) No 1902/2006 of the european parliament and of the council. 2006 Available from: http://data.europa.eu/eli/reg/2006/1902/oj/eng
  38. COM_COM(2017)0626_EN.pdf. 2017 Available from: https://www.europarl.europa.eu/RegData/docs_autres_institutions/commission_europeenne/com/2017/0626/COM_COM(2017)0626_EN.pdf [cited on March 17, 2024].
  39. Jin G. Wong S.T.C. Toward better drug repositioning: Prioritizing and integrating existing methods into efficient pipelines. Drug Discov. Today 2014 19 5 637 644 10.1016/j.drudis.2013.11.005 24239728
    [Google Scholar]
  40. Lazzerini M. Villanacci V. Pellegrin M.C. Martelossi S. Magazzù G. Pellegrino S. Lucanto M.C. Barabino A. Calvi A. Arrigo S. Lionetti P. Fontana M. Zuin G. Maggiore G. Bramuzzo M. Maschio M. Salemme M. Manenti S. Lorenzi L. Decorti G. Montico M. Ventura A. Endoscopic and histologic healing in children with inflammatory bowel diseases treated with thalidomide. Clin. Gastroenterol. Hepatol. 2017 15 9 1382 1389.e1 10.1016/j.cgh.2017.02.029 28286192
    [Google Scholar]
  41. An J Woodward JJ Sasaki T Minie M Elkon KB. Cutting edge: Antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction. J. Immunol. 194 9 4089 4093 10.4049/jimmunol.1402793
    [Google Scholar]
  42. Chen K. Schenone A.L. Borges N. Militello M. Menon V. Teaching an old dog new tricks: Colchicine in cardiovascular medicine. Am. J. Cardiovasc. Drugs 2017 17 5 347 360 10.1007/s40256‑017‑0226‑3 28353024
    [Google Scholar]
  43. Berking A.C. Flaadt T. Behrens Y.L. Yoshimi A. Leipold A. Holzer U. Lang P. Quintanilla-Martinez L. Schlegelberger B. Reiter A. Niemeyer C. Strahm B. Göhring G. Rare and potentially fatal - Cytogenetically cryptic TNIP1:PDGFRB and PCM1:FGFR1 fusion leading to myeloid/lymphoid neoplasms with eosinophilia in children. Cancer Genet. 2023 272-273 29 34 10.1016/j.cancergen.2023.01.002 36657267
    [Google Scholar]
  44. Nelson R.M. Conklin L.S. Komocsar W.J. Chen F. Williamson F. Crandall W.V. The role of master protocols in pediatric drug development. Ther. Innov. Regul. Sci. 2022 56 6 895 902 10.1007/s43441‑022‑00448‑3 36045315
    [Google Scholar]
  45. Muenster S. Zarragoikoetxea I. Moscatelli A. Balcells J. Gaudard P. Pouard P. Marczin N. Janssens S.P. Inhaled NO at a crossroads in cardiac surgery: Current need to improve mechanistic understanding, clinical trial design and scientific evidence. Front. Cardiovasc. Med. 2024 11 1374635 10.3389/fcvm.2024.1374635 38646153
    [Google Scholar]
  46. Servidei T. Sgambato A. Lucchetti D. Navarra P. Ruggiero A. Drug repurposing in pediatric brain tumors: Posterior fossa ependymoma and diffuse midline glioma under the looking glass. Front. Biosci. 2023 28 4 77 10.31083/j.fbl2804077 37114548
    [Google Scholar]
  47. Miera-Maluenda M. Pérez-Torres M. Mañas A. Rubio-San-Simón A. Butjosa-Espín M. Ruiz-Duran P. Seoane J.A. Moreno L. Segura M.F. Advances in the approaches used to repurpose drugs for neuroblastoma. Expert Opin. Drug Discov. 2024 19 11 1309 1319 10.1080/17460441.2024.2402413 39258785
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673291434250612050205
Loading
The Current and Potential Role of Pediatric Clinical Pharmacologists in Italy: A Review with Evidence Synthesis and Literature Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0109298673291434250612050205
/content/journals/cmc/10.2174/0109298673291434250612050205
/content/journals/cmc/10.2174/0109298673291434250612050205
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Pediatric clinical pharmacologist ; multidisciplinary team ; pediatrics ; therapeutic drug monitoring ; clinical pharmacology ; pharmacovigilance

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test