Maria Josep Cabañas Poy

Despite the progressive increase in obesity and associated chronic diseases in children, there is limited evidence on the optimal dosage of most medications for obese children and adolescents. This review analyzes the influence of pathophysiological changes on pharmacokinetics and pharmacodynamics and evaluates the body size descriptors used in clinical practice. Patients with obesity present significant pathophysiological alterations, such as a substantial increase in fat/lean mass ratio, increased blood flow and cardiac output, and changes in plasma protein binding, which may affect the volume of distribution of drugs and the adjustment of the loading dose. In these patients, the distribution volume of hydrophilic drugs appears to slightly increase, while it varies widely—depending on the drug and other factors such as affinity for other tissues—for lipophilic drugs. On the other hand, a reduction in tissue perfusion, alterations to liver enzyme activity, and an increase in liver and kidney mass and blood flow have been reported, indicating a possible modification in drug clearance and necessitating adjustments to maintenance regimens. Furthermore, while there are multiple size descriptors, it is difficult to establish a single dosing strategy for the obese population, given the lack of studies confirming the extent of changes in pharmacokinetic processes, which will also depend on the properties of each drug, such as liposolubility and elimination pathways. New strategies need to be developed to characterize pharmacokinetic and pharmacodynamic changes in the obese pediatric population in order to optimize dosing regimens and improve the safety and efficacy of treatments.

The integration of 3D printing (3DP) technologies into personalized medicine manufacture at the point-of-care is garnering significant interest due to its potential to create tailored drug products with precise dosages and other unique attributes. Both preclinical and clinical studies have demonstrated promising outcomes, including pharmacokinetic bioequivalence, improved patient acceptability, enhanced adherence, and the ability to produce consistent, reproducible dosage forms with accurate drug distribution. Some compounding pharmacies around the world are already incorporating 3DP into standard practice for simpler therapeutic treatments. However, further clinical evaluation is required for more complex treatments, such as multi-drug polypills. Conducting clinical trials involving 3DP technologies presents several challenges, including navigating evolving regulatory frameworks, addressing ethical and legal concerns, and complying with new point-of-care manufacturing guidelines. Although regulatory agencies are beginning to adapt their policies to accommodate 3DP, the absence of a comprehensive framework still creates uncertainty for pharmacists and healthcare providers. This article explores the planning and execution of clinical trials involving 3D printed medicines, with a focus on regulatory barriers, patient recruitment, compliance, and the integration of specialized equipment and expertise. It also discusses the implementation of 3DP for personalized drug manufacturing within hospital settings and offers guidance for obtaining clinical trial approval from the Spanish Agency for Medicine and Health Products (AEMPS). By providing these insights and recommendations, this article aims to support international harmonization and facilitate the adoption of 3DP technologies in clinical trials globally.

Background: This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in a real-world dataset of paediatric patients with inflammatory bowel disease (IBD). Methods: A descriptive, ambispective, single-centre study of paediatric patients with IBD who underwent IFX serum concentration measurements between September 2015 and September 2023. The patients received reactive TDM before September 2019 (n = 17) and proactive TDM thereafter (n = 21). We analysed for clinical, biological, and endoscopic remission; treatment failure; hospitalisations; emergency visits; and adverse drug reactions. The IFX doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, with specific targets for proactive TDM. Results: Of the 38 patients, 21 had Crohn’s disease (CD), 16 ulcerative colitis (UC), and 1 undetermined IBD. The mean (standard deviation) IFX trough concentrations were 6.83 (5.66) µg/mL (reactive) and 12.38 (9.24) µg/mL (proactive) (p = 0.08). No statistically significant differences between groups were found in remission rates or treatment failure. The proactive group had fewer hospitalisations (14.29% vs. 23.53%; p = 0.47) and shorter median hospitalisation days (6 vs. 19; p = 0.50), although the difference was not statistically significant. The number of patients with adverse reactions (infusion related reactions and infections) was higher in the proactive group (38.10% vs. 23.53%; p = 0.34) but the difference was not significantly different. Conclusions: Proactive TDM showed no significant differences in treatment outcomes compared to reactive TDM. However, the results in both the reactive and proactive TDM groups were not worse than those reported in other studies. Further studies with larger samples are needed to optimize the treatment strategies for pediatric IBD patients.

Background Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing. Objective The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance. Methods This observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d’Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM). Results Thirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (ADAM17) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, V_c, and V_p (central and peripheral distribution volumes) were 0.0066 L/h/46.4 kg, 0.0055 L/h/46.4 kg, 0.0081 L/h/46.4 kg, 0.0029 L/h/46.4 kg, 0.6750 L/46.4 kg, and 1.19 L/46.4 kg, respectively. The interindividual variability (IIV) estimates for clearance, V_c, and V_p were 19.33, 16.42, and 36.02%, respectively. Conclusions A popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.

To study the association between gestational age (GA) and weight at birth and the development of retinopathy of prematurity (ROP), and in particular the link between postnatal weight gain during th...

In response to the SARS-CoV-2 pandemic, the Hospital Pharmacy Services have quickly adapted to respond to a critical situation characterized by the constant and continuous admission of patients with severe pneumonia who needed treatment, requiring a transformation of the hospital in order to increase the number of hospital and critical beds. Moreover, other out-of-hospital spaces have been transformed into hospitalization units to absorb the large number of patients that had to be treated and isolated. To guarantee the distribution of medicines and the quality of the pharmaceutical care, drug distribution systems, such as unit dose and automated dispensing systems, have undergone transformations. Standard stocks were assigned for COVID units, and different dispensing circuits to avoid the risk of cross-contamination between COVID and non-COVID units were created, as well as disinfection protocols for medication transport systems and medication return protocols. All this without forgetting COVID treatment protocol's changes that were affected by the availability of the drugs. The increase in the number of beds in out-of-hospital spaces, such as field hospitals, hotels, socio-medical centers and nursing homes, has challenged Pharmacy Services, since new medication dispensing and conciliation circuits have been created forcing the increase of pharmacy staff's presence and modifying work shifts, to afford all the new tasks successfully. Development of contingency plans for the different Pharmacy Service activities and providing fluent communication channels are key elements for crisis situations or health emergencies such as the current pandemic.

The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily.