Special Issue "Development and Adaptation of New and Better Pediatric Drugs"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editor

Prof. Dr. José B. Fariña
E-Mail Website
Guest Editor
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC). Faculty of Pharmacy. Universidad de La Laguna. 38200 La Laguna. S/C de Tenerife. Spain
Interests: oral dosage forms; design and control; quality control; pediatrics medicines; drugs 3D printing

Special Issue Information

Dear Colleagues,

The combination of incentives and requirements established in recent years by drug regulatory agencies has allowed an increase in the quality, safety, and efficacy of medicines used in Pediatrics. However, this has not been sufficient and today, more than half of children are prescribed medicines whose posology is intended for an adult and which are not authorized for children, in the absence of a dosage form suitable for them. The absence of marketed medicines that meet the therapeutic needs of newborns or young children, mainly as regards the magnitude of the dose, pharmaceutical dosage form, and acceptance of the patient, justifies the individualization of treatments at different levels of care.

This Special Issue includes different alternatives for the development and adaptation of pharmacological treatments for pediatrics that come to cover therapeutic gaps because the drug does not exist with the proper dose or pharmaceutical dosage form and with the proper guarantees of quality, efficacy, and safety.

Prof. Dr. José B. Fariña
Guest Editor

Manuscript Submission Information

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Keywords

  • paediatric
  • extemporaneous
  • compounding
  • adapted formulation
  • authorized
  • quality control
  • stability
  • dosage forms
  • dose uniformity

Published Papers (6 papers)

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Research

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Article
Safety Testing of an Antisense Oligonucleotide Intended for Pediatric Indications in the Juvenile Göttingen Minipig, including an Evaluation of the Ontogeny of Key Nucleases
Pharmaceutics 2021, 13(9), 1442; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091442 - 10 Sep 2021
Viewed by 551
Abstract
The adult Göttingen Minipig is an acknowledged model for safety assessment of antisense oligonucleotide (ASO) drugs developed for adult indications. To assess whether the juvenile Göttingen Minipig is also a suitable nonclinical model for pediatric safety assessment of ASOs, we performed an 8-week [...] Read more.
The adult Göttingen Minipig is an acknowledged model for safety assessment of antisense oligonucleotide (ASO) drugs developed for adult indications. To assess whether the juvenile Göttingen Minipig is also a suitable nonclinical model for pediatric safety assessment of ASOs, we performed an 8-week repeat-dose toxicity study in different age groups of minipigs ranging from 1 to 50 days of age. The animals received a weekly dose of a phosphorothioated locked-nucleic-acid-based ASO that was assessed previously for toxicity in adult minipigs. The endpoints included toxicokinetic parameters, in-life monitoring, clinical pathology, and histopathology. Additionally, the ontogeny of key nucleases involved in ASO metabolism and pharmacologic activity was investigated using quantitative polymerase chain reaction and nuclease activity assays. Similar clinical chemistry and toxicity findings were observed; however, differences in plasma and tissue exposures as well as pharmacologic activity were seen in the juvenile minipigs when compared with the adult data. The ontogeny study revealed a differential nuclease expression and activity, which could affect the metabolic pathway and pharmacologic effect of ASOs in different tissues and age groups. These data indicate that the juvenile Göttingen Minipig is a promising nonclinical model for safety assessment of ASOs intended to treat disease in the human pediatric population. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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Article
Effects of the Off-Label Drug Prescription in the Paediatric Population in Spain from the Adoption of the Latest European Regulation: A Pre-Post Study
Pharmaceutics 2021, 13(4), 588; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13040588 - 20 Apr 2021
Cited by 1 | Viewed by 578
Abstract
The year 2021 marks the 15th anniversary of the Paediatric Regulation (1901/2006/EC) in Europe. The main aim of the study was to conduct a pre-post comparison on the annual off-label prescription rates in the under-18 population in Spain and assess the potential influence [...] Read more.
The year 2021 marks the 15th anniversary of the Paediatric Regulation (1901/2006/EC) in Europe. The main aim of the study was to conduct a pre-post comparison on the annual off-label prescription rates in the under-18 population in Spain and assess the potential influence of the Paediatric Regulation adoption. An observational study in the paediatric population was performed. Four cross-sectional annual periods, one before and the three latest periods after the adoption of the Regulation, were compared. Prescriptions in the primary health care setting were sorted by age group and drug and off-label status were determined. The number of off-label prescriptions issued by paediatricians was over two million per year. Prior to the adoption of the Paediatric Regulation, the off-label prescription rate was estimated at 7% of total prescriptions. Although the increase in the off-label rate over the study periods was mild, it was statistically significant (OR: 1.045; 95% CI: 1.043–1.046; p < 0.05). One of the most vulnerable population groups was neonates and infants up to 1 year, in which the off-label prescription rates showed the highest increase during the post follow-up period, which was statistically significant (OR: 4.270; 95% CI: 4.253–4.287; p < 0.05). The findings can help raise awareness and advocate for the development and authorization of medicines for children in the primary health care setting. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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Article
Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology
Pharmaceutics 2021, 13(4), 470; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13040470 - 30 Mar 2021
Viewed by 597
Abstract
Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic [...] Read more.
Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC/MS2 analysis, was used to develop a population pharmacokinetic model (Monolix® software). A mono-compartmental model with first-order absorption and elimination best fit the data. The only covariate retained for the final model was “body surface area” (D1 and D8). The model also demonstrated that 1.5 mg/m2 would be the recommended sirolimus dose for further studies and that steady-state TDM is necessary to adjust the dosing regimen in atypical profiles (36.4% of the population). No correlation was found between sirolimus trough concentrations and efficacy and/or observed toxicities. The study reveals the relevance of sirolimus TDM in pediatric oncology as it is needed in organ transplantation. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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Article
Adherence and Acceptability of an Oral Antibiotic Used for the Prevention of Pediatric Urinary Tract Infection in Japan
Pharmaceutics 2021, 13(3), 345; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030345 - 06 Mar 2021
Viewed by 502
Abstract
Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity [...] Read more.
Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity that is associated with renal scarring. Acceptability is likely to have a significant impact on patient adherence. Herein we used a validated data-driven approach—the ClinSearch acceptability score test (CAST)—to investigate the acceptability of cefaclor, an oral antibiotic widely used for the prevention of pediatric UTI in Japan. Standardized observer reports were collected for 58 intakes of cefaclor 10% fine granules in patients aged from 0 to 17 years. The medicine was classified as positively accepted on the acceptability reference framework. According to the percentage of the prescribed dose taken reported at the end of the treatment, patients exhibited good adherence to this well-accepted medicine. Nonetheless, requirements for greater dosing frequency or poor acceptability in certain patients could affect adherence. Acceptability should be established to ensure patient adherence to medicines used for long-term prophylaxis and consequently guarantee the safety and efficacy of the treatment. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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Article
Acceptability of a Sublingual Drug Formulation for Respiratory Tract Infections in Children Aged 3 to 5 Years
Pharmaceutics 2021, 13(2), 294; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020294 - 23 Feb 2021
Cited by 1 | Viewed by 706
Abstract
In pediatrics, acceptability has emerged as a key factor for compliance, and consequently for treatment safety and efficacy. Polyvalent mechanical bacterial lysate (PMBL) in 50-mg sublingual tablets is indicated in children and adults for the prophylaxis of recurrent respiratory tract infections. This medication [...] Read more.
In pediatrics, acceptability has emerged as a key factor for compliance, and consequently for treatment safety and efficacy. Polyvalent mechanical bacterial lysate (PMBL) in 50-mg sublingual tablets is indicated in children and adults for the prophylaxis of recurrent respiratory tract infections. This medication may be prescribed in children over 3 years of age; the appropriateness of this sublingual formulation should thus be demonstrated amongst young children. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for medication intake over the course of treatment (days 1, 2, and 10) in 37 patients aged 3 to 5 years, and then analyzed in an intelligible model: the acceptability reference framework. According to this multidimensional model, 50-mg PMBL sublingual tablets were classified as “positively accepted” in children aged 3 to 5 years on all three days of evaluation. As the acceptability evaluation should be relative, we demonstrated that there was no significant difference between the acceptability of these sublingual tablets and a score reflecting the average acceptability of oral/buccal medicines in preschoolers. These results highlight that sublingual formulations could be appropriate for use in preschoolers. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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Review

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Review
Excipients in the Paediatric Population: A Review
Pharmaceutics 2021, 13(3), 387; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030387 - 13 Mar 2021
Cited by 4 | Viewed by 1213
Abstract
This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used [...] Read more.
This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied. Full article
(This article belongs to the Special Issue Development and Adaptation of New and Better Pediatric Drugs)
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