(1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected from 1204 patients included in a therapeutic drug monitoring program were retrospectively analyzed. Patients were randomly assigned to either a model development group or an external evaluation group. PopPK analysis was performed on 1751 samples from 776 patients with NONMEM using a nonlinear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment and comedication variables on the apparent clearance (CL/F) of VPA was studied. The bootstrap method was used to evaluate the final model internally. External evaluation was carried out using 776 VPA serum samples from 368 patients. (3) Results: A one-compartment model with first-order absorption and elimination successfully described the data. The final model included total body weight, age and comedication with phenytoin, phenobarbital and carbamazepine with a significant impact on VPA elimination. Internal and external evaluations demonstrated the good predictability of the model. (4) Conclusions: A PopPK model of VPA in Caucasian patients was successfully established, which will be helpful for model-informed precision dosing approaches in clinical patient care.

The medication in an electronic prescribing system (EPS) does not always match the patient’s actual medication. This prospective study analyzes the discrepancies (any inconsistency) between medication prescribed using an EPS and the medication revised by the clinical pharmacist upon admission to the observation area of the emergency department (ED). Adult patients with multimorbidity and/or polypharmacy were included. The pharmacist used multiple sources to obtain the revised medication list, including patient/carer interviews. A total of 1654 discrepancies were identified among 1131 patients. Of these patients, 64.5% had ≥1 discrepancy. The most common types of discrepancy were differences in posology (43.6%), commission (34.7%), and omission (20.9%). Analgesics (11.1%), psycholeptics (10.0%), and diuretics (8.9%) were the most affected. Furthermore, 52.5% of discrepancies affected medication that was high-alert for patients with chronic illnesses and 42.0% of medication involved withdrawal syndromes. Discrepancies increased with the number of drugs (ρ = 0.44, p < 0.01) and there was a difference between non-polypharmacy patients, polypharmacy ones and those with extreme polypharmacy (p < 0.01). Those aged over 75 years had a higher number of prescribed medications and discrepancies occurred more frequently compared with younger patients. The number of discrepancies was larger in women than in men. The EPS medication record requires verification from additional sources, including patient and/or carer interviews.

El objetivo principal fue diseñar y realizar una práctica de la asignatura “Atención Farmacéutica” de 4º curso del Grado en Farmacia, compatibilizando el aprendizaje con la prestación de un servicio de atención farmacéutica a personas mayores. Como objetivo secundario se planteó estudiar la adherencia de los participantes a sus tratamientos. En el curso 2022/2023 se diseñó la práctica y se ensayó con 20 estudiantes voluntarios como un proyecto de Aprendizaje-Servicio. En 2023/2024 se implementó en el programa de la asignatura participando los 61 estudiantes matriculados. En total, se realizaron 8 visitas a centros de día, coordinadas a través del Programa de Acercamiento Intergeneracional del Servicio de Asuntos Sociales de la USAL. Participaron 141 personas mayores que respondieron de forma positiva a la actividad, apreciando su utilidad y expresando su interés en más iniciativas de este tipo. Se consideraron adherentes el 57 % de los participantes. Contestaron la encuesta anónima de satisfacción 41 estudiantes, considerando más del 80% la experiencia beneficiosa, a nivel personal y académico. La actividad diseñada ha demostrado ser viable y cumplir con los objetivos planteados. La satisfacción de los estudiantes, personas mayores, profesores y coordinadoras de los centros resalta la importancia de este tipo de iniciativas.

El ácido valproico es un fármaco utilizado en el tratamiento de la epilepsia y otros trastornos neurológicos cuya elevada variabilidad farmacocinética y estrecho margen terapéutico justifican su monitorización terapéutica. El objetivo fue implementar un modelo farmacocinético poblacional de ácido valproico en el software en desarrollo WinPKS y evaluar su capacidad predictiva en pacientes epilépticos adultos monitorizados en la práctica clínica. El estudio incluyó 65 pacientes en tratamiento en monoterapia o biterapia con carbamazepina o fenitoína. Se estimaron parámetros farmacocinéticos mediante una estimación “a priori”, basada en el modelo poblacional, y una estimación bayesiana, que combina dicha información con las concentraciones plasmáticas de fármaco en cada paciente. La capacidad predictiva se valoró comparando concentraciones observadas y predichas mediante la estimación de distintos tipos de error. Los resultados muestran una mejora en la predicción de concentraciones con algoritmos bayesianos frente al método “a priori”, con menor error relativo y mejor correlación entre concentraciones observadas y predichas. Se confirma el efecto inductor de carbamazepina y fenitoína sobre la eliminación del ácido valproico. Además, se desarrolló una aplicación web (VpaOptim) que simula perfiles concentración‑tiempo del fármaco a partir del modelo farmacocinético poblacional, útil para la individualización posológica del ácido valproico en el ámbito clínico.

Background: Subcutaneous infliximab (SC-IFX) represents a significant advance for patients with inflammatory bowel disease (IBD) due to the possibility of home self-administration. However, at this time, there are no clear recommendations for implementing model-informed precision dosing (MIPD) in accordance with real-world clinical knowledge. Objective: The aim of the present study is to develop a population pharmacokinetic (PopPK) model for SC-IFX. Methods: A multicenter retrospective observational study was performed in adult patients (both naïve patients and those switched from intravenous administration) diagnosed with IBD. PopPK analysis was performed using NONMEM with a nonlinear mixed-effects model approach. A stepwise covariate modeling approach was implemented to identify anthropometric and clinical factors influencing SC-IFX disposition. The bootstrap method was used for internal model validation. Results: A total of 250 serum concentration samples of IFX, corresponding to 45 patients, were analyzed. A one-compartment model with first-order absorption adequately described the data. The final model included total body weight and suspected immunogenicity as covariates of clearance (CL). Suspected immunogenicity was associated with a 70.0% increase in clearance, while each kg deviation from the median weight (73 kg) modified clearance by 0.888%/kg. Conclusions: A PopPK model for SC-IFX was successfully developed and validated using European real-world data. This exploratory model establishes a foundation for future MIPD applications, offering a structured approach to initiate or transition patients to SC-IFX therapy.