Artículos (Farmacología)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11025

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Advanced sporadic renal epithelioid angiomyolipoma: Case report of an extraordinary response to sirolimus linked to TSC2 mutation
(Springer Nature, 2018-05-15) Espinosa, Marta; Roldán-Romero, Juan María; Durán, Ignacio; Álava Casado, Enrique de; Apellaniz-Ruiz, María; Cascón, Alberto; Garrigós, Carmen; Robledo, Mercedes; Rodríguez-Antona, Cristina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Economia, Industria y Competitividad (MINECO). España
Background: Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined. Case presentation: Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation. Conclusion: NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs.
Influence of Pharmacist Intervention, Based on CMO Model, to Improve Activation in HIV Patients
(Sociedad Española de Quimioterapia, 2029) Morillo Verdugo, Ramón Alejandro; Robustillo Cortés, María de las Aguas; Manzano García, Mercedes; Almeida González, Carmen V.; Universidad de Sevilla. Departamento de Farmacología
Objectives. The aim of study was to evaluate the influence of pharmacist intervention based on “CMO model”, to improve activation in HIV-patients. Material and methods. Longitudinal, prospective, single- center study. Eligible patients were HIV-infected, taking antiretroviral treatment. The collected data included demographic characteristics, clinical and HIV-related and pharmacotherapeutic variables. The primary outcome was the variation of patient activation measured by Spanish adapted patient activation measure questionnaire. This questionnaire assesses people’s knowledge, skills and confidence in managing their own health care. The assessment was performed at the beginning and 6 months after the program start, which consisted of individualized interventions planned in the stratification model, a motivational interview and a specific pharmacotherapeutic follow-up. Results. A total of 140 patients were included. The most common regimens prescribed were based on non-nucleoside plus nucleoside reverse transcriptase inhibitor (44.0%) and more than half of the patients had chronic concomitant medication. The patients who achieved the highest activation level increased from 28.1% to 68.3% (p<0.0005). The relationship between this increase in patient activation and the stratification level that occurs in largest increases in patients with a low need level, where it was observed an improvement in the percentage of patients with high activation from 28.3% to 74.3% (p<0.001) after intervention. The percentage of patients with adequate adherence to concomitant treatment increased by 18.4% (p = 0.035). Baseline PAM values showed high activation for 28.6% (40 patients), intermediate for 43.6% (61) and low for 27.9% (39). Conclusion. CMO model has an important role for patient activation, improving adherence and health outcomes for HIV+ patients.
Concordance between Pharmacotherapeutic Complexity Calculated and Perceived by HIV+ Patients with Antiretroviral Treatment
(Elsevier, 2019) Manzano García, Mercedes; Serrano Giménez, Reyes; Robustillo Cortés, María de las Aguas; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Objective: To determine the difference between the pharmacotherapeutic complexity index by Medication Regimen Complexity Index and it's perceived by patients through a visual analogue scale in patients HIV+ with antiretroviral treatment. Method: Prospective, observational study of patients HIV+ > 18 years of age with stable antiretroviral treatment in the last three months, followed up by external consultations of pharmaceutical care between October’17 and February’18. The main variable of the study was the concordance between the median of the score obtained in the pharmacotherapeutic complexity perceived by the patients using the visual analog scale whose range of values oscillates between 0–10, categorized in low complexity (0–1) and high complexity (2–10), and the median of the score obtained for the theoretical pharmacotherapeutic complexity using the Medication Regimen Complexity Index tool whose ranges of values oscillate between 1 and infinity, categorized in low complexity (0–11) and high complexity > 11. The overall complexity was calculated: antiretroviral treatment and concomitant treatment. Results: We included 236 patients in the study. There was a discrete concordance between the pharmacotherapeutic complexity perceived by the patients and that calculated according to the Medication Regimen Complexity Index tool (Cohen's Kappa index 0.203). The median of the Medication Regimen Complexity Index of the total medication was 6 (interquartile range: 4–10) versus the median of the Complexity Index measured by visual analog scale of 2 (interquartile range: 0–4). Conclusions: Patients perceive a pharmacotherapeutic complexity lower than that calculated. Therefore, we must include the two scales in pharmaceutical care for a better understanding of the patient's perception.
Determination of a Cutoff Value for Medication Regimen Complexity Index to Predict Polypharmacy in HIV+ Older Patient
(Sociedad Española de Quiminoterapia, 2019) Morillo Verdugo, Ramón Alejandro; Robustillo Cortés, María de las Aguas; Abdel-Kader Martín, Laila; Álvarez de Sotomayor Paz, María; Lozano de León Naranjo, Fernando; Almeida González, Carmen V.; Universidad de Sevilla. Departamento de Farmacología
Introduction. HIV+ patients have increased their life expectancy with a parallel increase in age-associated co-morbidities and pharmacotherapeutic complexity. The aim of this study was to determine an optimal cutoff value for Medication regimen complexity index (MRCI) to predict polypharmacy in HIV+ older patients Patients and methods. A transversal observational single cohort study was conducted at a tertiary Hospital in Spain, between January 1st up to December 31st, 2014. Patients included were HIV patients over 50 years of age on active antiretroviral treatment. Prevalence of polypharmacy and it pattern were analyzed. The pharmacotherapy complexity value was calculated through the MRCI. Receiver operating characteristic curve analyses were used to calculate the area under the curve (AUC) for the MRCI value medications to determine the best cutoff value for identifying outcomes including polypharmacy. Sensitivity and specificity were also calculated. Results. A total of 223 patients were included. A 56.1% of patients had polypharmacy, being extreme polypharmacy in 9.4% of cases. Regarding the pattern of polypharmacy, 78.0% had a cardio-metabolic pattern, 12.0% depressive-psychogeriatric, 8.0% mixed and 2.0% mechanical-thyroidal. The ROC curve demonstrated that a value of medication complexity index of 11.25 point was the best cutoff for predict polypharmacy (AUC=0.931; sensitivity= 77.6%; specificity= 91.8%). Conclusions. A cut-off value of 11.25 for MRCI is proposed to determine if a patient reaches the criterion of polypharmacy. In conclusion, the concept of polypharmacy should include not only the number of prescribed drugs but also the complexity of them.
Medication Adherence and Glycemic Control in Older Adults with Type 2 Diabetes: A Cross-Sectional Study in a Community Setting
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-04-23) Nascimento, Tânia; Andrade, Amanda; Pinto, Ezequiel; Cabrita, Catarina; Pais, Sandra; Puerta Vázquez, Rocío de la; Universidad de Sevilla. Departamento de Farmacología
Background/Objectives: Glycemic control is essential for preventing both short- and long-term complications of type 2 diabetes (T2D), requiring strict adherence to pharmacological therapy. Medication adherence directly influences therapeutic effectiveness, making its assessment in clinical practice crucial. This study aimed to evaluate medication adherence in elderly patients with T2D and its association with glycemic control. Methods: A descriptive cross-sectional study was conducted in the Algarve, Portugal, involving 133 elderly patients (≥60 years) with T2D. Cardiometabolic parameters and medication adherence (global, intentional, and unintentional) were assessed. Statistical analyses were performed using IBM SPSS Statistics 28.0. Results: The study population had a mean age of 71.7 ± 5.7 years, with a predominance of male participants (57.9%) and a high prevalence of dyslipidemia and/or hypertension. Cardiometabolic control was generally poor, with only 26.3% achieving blood pressure targets (≤140/90 mmHg), 8.5% maintaining fasting glycemia within the recommended range (70–110 mg/dL), and 13.6% attaining glycated hemoglobin (HbA1c) values ≤ 7%. Despite this, medication adherence was notably high (97.7%), with no significant association with cardiometabolic control (p > 0.05). Unintentional non-adherence behaviors, such as forgetfulness and inconsistent medication schedules, were the most frequently reported. Conclusions: Although elderly patients with T2D demonstrated high medication adherence rates, their cardiometabolic control remained suboptimal. Unintentional non-adherence behaviors may contribute to poor glycemic control. However, medication adherence alone does not fully explain these outcomes, highlighting the need to assess adherence to other self-care behaviors, particularly dietary and physical activity patterns. Future interventions should integrate comprehensive lifestyle modifications alongside pharmacological management to enhance overall disease control.
Synthesis, Characterization, and Preliminary In Vitro Anticancer Activity of Zinc Complexes Containing Amino Acid-Derived Imidazolium-Based Dicarboxylate Ligands
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-03-30) Carrasco Carrasco, Carlos Jesús; Pastor Navarro, Antonio; Conejo Argandoña, María del Mar; Álvarez González, Eleuterio; Calderón Montaño, José Manuel; López Lázaro, Miguel; Galindo del Pozo, Agustín; Universidad de Sevilla. Departamento de Química Inorgánica; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España
Coordination polymers containing zinc and imidazolium-based dicarboxylate ligands, [LR]−, were synthesized by reacting zinc acetate with HLR compounds, 1. The resulting complexes were characterized and structurally identified using single-crystal X-ray diffraction, revealing polymeric structures for the complexes [Zn(LR)2]n (R = Gly, 2a; βAla, 2b) and [Zn(LLeu)2(H2O)2]n (2c). In these structures, the [LR]− ligands adopt a bridging monodentate μ-κ1-O1,κ1-O3 coordination mode, resulting in distorted tetrahedral (2a, 2b) or octahedral (2c) geometries around the zinc center. When the synthesis was carried out in the presence of amino acids, mixed ligand complexes [Zn(LR)(aa)(H2O)]n (R = aa = Val, 2d, and R = aa = Ile, 2e) were formed. Complexes 2d–2e were also structurally characterized using single-crystal X-ray crystallography, revealing that the ligand [LR]− maintained the same coordination mode, while the zinc center adopted a five-coordinated geometry. The cytotoxic activity of complexes 2a–2e was evaluated against three cancer cell lines and one non-cancerous cell line. Remarkably, these complexes exhibited higher toxicity against cancer cells than against the non-cancerous cell line, and they showed greater selectivity than carboplatin, a commonly used chemotherapy drug. Although, in general, these complexes did not surpass the selectivity of gemcitabine, complex 2c stood out for exhibiting a selectivity index value similar to that of gemcitabine against melanoma cells. Among the series, compounds 2a–2c demonstrated the highest activity, with 2a being the only complex with some selective activity against lung cancer. Complex 2b was the most active, though with low selectivity, while complex 2c exhibited the highest selectivity for melanoma and bladder cancer (selectivity index of 3.0).
Loss of efficacy and safety of the switch from infliximab original to infliximab biosimilar (CT-P13) in patients with inflammatory bowel disease
(Baishideng Publishing Group Inc, 2018-12-14) Guerra Veloz, María Fernanda; Argüelles Arias, Federico; Laria, Luisa Castro; Maldonado Pérez, Belén; Benítez Roldán, Antonio; Perea Amarillo, Raúl; Merino Bohórquez, Vicente; Calleja, Miguel Ángel; Caunedo Álvarez, Ángel; Vilches Arenas, Ángel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. CTS312: Análisis de la Demanda Sanitaria
BACKGROUND Infliximab original has changed the natural history of inﬂammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.
Transforming Respiratory Diseases Management: a CMO-based Hospital Pharmaceutical Care Model
(Frontiers Media SA, 2024) Zarate Tamames, Borja; Garin, Noé; Calvin Lamas, Marta; Jornet, Sonia; Martínez Simón, José J.; Garcia-Gil, Sara ; García Rebolledo, Eva M.; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Introduction: Respiratory diseases encompass a diverse range of conditions that significantly impact global morbidity and mortality. While common diseases like asthma and COPD exhibit moderate symptoms, less prevalent conditions such as pulmonary hypertension and cystic fibrosis profoundly affect quality of life and mortality. The prevalence of these diseases has surged by approximately 40% over the past 3 decades. Despite advancements in pharmacotherapy, challenges in drug administration, adherence, and adverse effects persist. This study aimed to develop and perform an interim validation of a Capacity-Motivation-Opportunity (CMO) model tailored for respiratory outpatients to enhance pharmaceutical care, which is the direct, responsible provision of medication-related care for the purpose of achieving definite outcomes that improve a patient’s quality of life, and overall wellbeing. Methodology: This cross-sectional, multicenter study was conducted from March 2022 to March 2023. It comprised four phases: 1) forming an expert panel of 15 hospital pharmacists, 2) selecting respiratory pathologies based on prevalence and severity, 3) developing the CMO model’s pillars, and 4) integrating and conducting an interim validation of the model. The Capacity pillar focused on patient stratification and personalized care; the Motivation pillar aligned therapeutic goals through motivational interviewing; and the Opportunity pillar promoted the use of information and communication technologies (ICTs) for telemedicine. Results: The model included eight respiratory diseases based on expert assessment. For the Capacity pillar, 22 variables were defined for patient stratification, leading to three priority levels for personalized pharmaceutical care. In a preliminary test involving 201 patients across six hospitals, the stratification tool effectively classified patients according to their needs. The Motivation pillar adapted motivational interviewing techniques to support patient adherence and behavior change. The Opportunity pillar established teleconsultation protocols and ICT tools to enhance patient monitoring and care coordination. Conclusion: The CMO model, tailored for respiratory patients, provides a comprehensive framework for improving pharmaceutical care. By focusing on patient-centered care, aligning therapeutic goals, and leveraging technology, this model addresses the multifaceted needs of individuals with respiratory conditions. Future studies are necessary to validate this model in other healthcare systems and ensure its broad applicability.
Dual Trajectories of Polypharmacy and Medication Regimen Complexity Index in People Living with HIV in Spain
(Elsevier, 2024) Contreras Macías, Enrique; Robustillo Cortés, María de las Aguas; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Background: Polypharmacy, using 6 or more medications, may increase the risk of high medication regimen complexity index (MRCI). We aimed to identify the interrelationship between trajectories of polypharmacy and MRCI. Methods: People living with HIV (PLWH) (aged ≥ 18) were included in from 2010 to 2021. Group-based trajectory modeling (GBTM) was used to identify polypharmacy trajectories and the complexity index of the medication regimen and the dual GBTM to identify their interrelationship. Results: In total, 789 participants who met the eligibility criteria were included in the study, with a median age of 47 years. GBTM analysis was used to reveal latent polypharmacy trajectories among PLWH. The findings disclosed four distinctive trajectories, with the majority (50.8%) of the PLWH falling into the ‘low increasing’ trajectory. Furthermore, GBTM identified 2 trajectories characterized by high MRCI, and a substantial proportion (80.2%) was assigned to the ‘slightly increasing low’ trajectory group. The study revealed that younger age (< 50 years) was a significant predictor of membership in the ‘consistently low’ trajectory, while male gender was associated with the groups of ‘low increasing’ and ‘moderately decreasing’ polypharmacy trajectory. Conclusions: GBTM failed to discern a discernible interrelationship between polypharmacy and the high MRCI. It is imperative to undertake future studies within this research domain, considering potential effect modifiers, notably the specific type of concomitant drug. This approach is crucial due to the outcomes induced by both polypharmacy and the magnitude of the pharmacotherapeutic complexity in PLWH.
Uncuarto de siglo del grupo VIH-SEFH: transformando la atención, afrontando retos y reafirmando el compromiso
(Elsevier, 2024) Morillo Verdugo, Ramón Alejandro; Taberner Bonastre, Pilar; Universidad de Sevilla. Departamento de Farmacología
Análisis de los costes asociados a la administración intramuscular versus oral de la terapia antirretroviral en el manejo de la infección por el virus de la inmunodeficiencia humana
(Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica, 2024) Estrada, Vicente; Losa, Juan Emilio; Morillo Verdugo, Ramón Alejandro; Pérez Encinas, Montserrat; Santos, Jesús; Castro, Antonio; Presa González, María; Salinas Ortega, Laura; Universidad de Sevilla. Departamento de Farmacología
Objetivo: Identificar y analizar los recursos y costes asociados a la administración deltratamiento antirretroviral (TAR) cabotegravir + rilpivirina (CAB + RPV) intramuscular frente al TAR oral en el manejo de la infección por el virus de la inmunodeficiencia humana tipo I (VIH-1), en Espana. Métodos: Se desarrolló un modelo para la identificación de recursos y análisis de costes desde la perspectiva del Sistema Nacional de Salud (SNS) y de la sociedad asociado a la administración del TAR intramuscular (CAB + RPV) frente al TAR oral en un horizonte temporal de 2 anos. ˜ Los costes englobaron la monitorización por cambio de tratamiento, la dispensación farmacéutica, la administración, el manejo de los eventos adversos por reacciones en el lugar de inyección (EAs-RLI), el desplazamiento al centro hospitalario, el servicio de telefarmacia y la pérdida de productividad laboral. Los costes unitarios (D , 2023) se obtuvieron de la literatura. Se realizaron análisis de sensibilidad para evaluar la robustez del modelo. Resultados: El TAR intramuscular frente al TAR oral se asoció con un incremento de los costes de 673,16 D /paciente en 2 anos ˜ desde la perspectiva del SNS y de 719,59 D /paciente desde la perspectiva social. El TAR intramuscular generaría un incremento de costes de dispensación (+97,75 D ), administración (+394,55 D ), monitorización (+288,74D ), manejo de los EAs-RLI (+6,46 D ), desplazamiento (+8,36 D ) y pérdida de productividad laboral (+38,07 D ), respecto a la administración del TAR oral. Conclusiones: El tratamiento del VIH-1 con CAB + RPV intramuscular implica un aumento del consumo de recursos y costes, frente al TAR oral.
Influence of carbon nanotubes on the antimicrobial character of the β-lactam antibiotics Cefepime and Meropenem
(Elsevier, 2025-05) Bernal Pérez, Eva; Mata Hijosa, Laura; López-Cornejo, María del Pilar; Moyá Morán, María Luisa; Madinabeitia, Nuria; Merino Bohórquez, Vicente; López-López, Manuel; Lebrón Romero, José Antonio; Universidad de Sevilla. Departamento de Química Física; Universidad de Sevilla. Departamento de Farmacología
The overuse of antibiotics over decades has led to a multi-resistance of bacteria that today poses a serious threat to human health. β-lactam antibiotics are one of the most prescribed drugs against bacterial infectious diseases, which has conducted to increased resistance. The short half-life of these drugs results in low bioavailability, which limits their clinical use and requires continuous administration by infusion. Encapsulation of these antibiotics in nanocarriers would improve their biopharmaceutical properties by protecting them. With this in mind, single- and multi-walled carbon nanotubes (SWCNTs and MWCNTs, respectively) were used here as nanocarriers for the antibiotics Meropenem and Cefepime. The adsorption process of these antibiotics in the carbon nanotubes (CNTs) was optimized to obtain a high encapsulation efficiency. The complexes CNT/drug prepared were characterized by dynamic light scattering and spectroscopic measurements. The growth of Escherichia coli and Staphylococcus aureus bacteria was analyzed in the presence of the CNT/drug complexes to evaluate the pharmacological properties of the encapsulated antibiotics. Results showed lower minimum inhibitory concentration (MIC) values of the CNT/drug complexes compared to free drugs. This indicates the preservation of the pharmacological properties of the encapsulated antibiotics. In addition, the stability of the encapsulated antibiotics was observed to last at least 24 h, which was a great improvement compared to the free drugs.
Role of inorganic phosphate concentrations in in vitro activity of fosfomycin
(Elsevier, 2022-02) Ortiz Padilla, Miriam; Portillo Calderón, Inés María; Maldonado, Natalia; Rodríguez Martínez, José Manuel; De Gregorio Iaria, Belén; Merino Bohórquez, Vicente; Rodríguez-Baño, Jesús; Pascual Hernández, Álvaro; Docobo Pérez, Fernando; Universidad de Sevilla. Departamento de Microbiología; Universidad de Sevilla. Departamento de Genética; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III; European Union (UE); Universidad de Sevilla. BIO116: Genética Bacteriana; Universidad de Sevilla. CTS210: Resistencia a Antimicrobianos
Objectives: The objective of this study was to evaluate the in vitro activity of fosfomycin under different physiological concentrations of inorganic phosphate (Pi). Methods: The wild-type BW25113 strain, four isogenic mutants (ΔglpT, ΔuhpT, ΔglpT-uhpT, and ΔphoB) and six clinical isolates of Escherichia coli with different fosfomycin susceptibilities were used. EUCAST breakpoints were used. Susceptibility was evaluated by agar dilution using standard Mueller–Hinton agar (Pi concentration of 1 mM similar to human plasma concentration) and supplemented with Pi (13 and 42 mM, minimum and maximum urinary Pi concentrations) and/or glucose-6-phosphate (25 mg/L). Fosfomycin transporter promoter activity was assayed using PglpT::gfpmut2 or PuhpT::gfpmut2 promoter fusions in standard Mueller–Hinton Broth (MHB), supplemented with Pi (13 or 42 mM) ± glucose-6-phosphate. Fosfomycin activity was quantified, estimating fosfomycin EC50 under different Pi concentrations (1, 13 and 42 mM + glucose-6-phosphate) and in time–kill assays using fosfomycin concentrations of 307 (maximum plasma concentration (Cmax)), 1053 and 4415 mg/L (urine Cmax range), using MHB with 28 mM Pi (mean urine Pi concentration) + 25 mg/L glucose-6-phosphate. Results: All the strains showed decreased susceptibility to fosfomycin linked to increased Pi concentrations: 1–4 log2 dilution differences from 1 to 13 mM, and 1–8 log2 dilution differences at 42 mM Pi. Changes in phosphate concentration did not affect the expression of fosfomycin transporters. By increasing Pi concentrations higher fosfomycin EC50 bacterial viability was observed, except against ΔglpT-uhpT. The increase in Pi reduced the bactericidal effect of fosfomycin. Discussion: Pi variations in physiological fluids may reduce fosfomycin activity against E. coli. Elevated Pi concentrations in urine may explain oral fosfomycin failure in non-wild-type but fosfomycin-susceptible E. coli strains.
Activity of Fosfomycin and Amikacin against Fosfomycin-Heteroresistant Escherichia coli Strains in a Hollow-Fiber Infection Model
(ASM Journals, 2021-04-19) Portillo Calderón, I.; Ortiz Padilla, Miriam; De Gregorio Iaria, Belén; Merino Bohórquez, Vicente; Blázquez, J.; Rodríguez-Baño, Jesús; Rodríguez Martínez, José Manuel; Pascual Hernández, Álvaro; Docobo Pérez, Fernando; Universidad de Sevilla. Departamento de Microbiología; Universidad de Sevilla. Departamento de Genética; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. BIO116: Genética Bacteriana; Universidad de Sevilla. CTS210: Resistencia a Antimicrobianos
We evaluated human-like the efficacy of intravenous doses of fosfomycin of 8 g every 8 h (8 g/Q8h) and of amikacin (15 mg/kg/Q24h) in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM). Six fosfomycin-heteroresistant E. coli isolates (four with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100 mg/liter), fosfomycin (50 and 200 mg/liter), and amikacin (32 mg/liter) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip assay (GSA), and broth microdilution (BMD). Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. The efficacies of fosfomycin (8 g/Q8h) and amikacin (15 mg/kg/Q24h) alone and in combination were assessed using an HFIM. Five isolates were determined to be resistant to fosfomycin by AD and BMD, but all were determined to be susceptible by GSA. All isolates were determined to be susceptible to amikacin. Antibiotic combinations were synergistic in two isolates, and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64 mg/liter, although at 307 mg/liter only the normomutators and two hypermutators survived. Four isolates survived under 16 mg/liter amikacin, and none survived at 45 mg/liter. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilize bacterial cultures; however, the combination of fosfomycin and amikacin yielded a rapid eradication. There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the amikacin-fosfomycin combination can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.
Triacylglycerol Composition of Seed Oil from Corema album Berries
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-16) Martín Cordero, Carmen; Martínez-Force, Enrique; Acero de Mesa, Nuria; Muñoz-Mingarro, Dolores; León González, Antonio José; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España
The seeds of Corema album are considered a by-product in fruit processing. This study aimed to determine the oil contents in seeds and characterize their triacylglycerol contents through a comparative analysis using three extraction solvent systems: hexane (Soxhlet method), hexane–isopropanol (Hara–Radin method), and methanol–chloroform–water (Bligh–Dyer method). The extracts were analyzed by gas chromatography/mass spectrometry and HPLC. The composition of fatty acids and triacylglycerols was determined, as were the allocation of fatty acids across the sn-2 and sn-1,3 positions, tocopherol and tocotrienol profile, and melting behavior through differential scanning calorimetry. Furthermore, the atherogenicity (IA) and thrombogenicity (IT) cardiovascular health indices were also calculated. The oil predominantly contained unsaturated fatty acids, and α-linolenic acid made up 45.8% of the total, along with a reduced n-6/n-3 fatty acid ratio (0.75). The α-linolenoyl chain primarily occupied the sn-1,3 (45.9%) and sn-2 (39.1%) positions. γ-tocotrienol was the most abundant tocochromanol. The melting curve of oil suggests the presence of fractions with a low melting point, composed of triacylglycerols containing polyunsaturated fatty acids. The oil exhibits low values for IA and IT of 0.05 and 0.04, respectively. Corema seed oil has potential health benefits thanks to its rich composition in the essential fatty acid, α-linolenic acid, the low proportion of n-6/n-3 fatty acids, and the low values of IA and IT.
Misleading nomenclature in the IARC Monographs Programme: a straightforward solution to improve accuracy and clarity
(Open Exploration Publishing, 2025-02-07) López Lázaro, Miguel; Universidad de Sevilla. Departamento de Farmacología
The International Agency for Research on Cancer (IARC) Monographs Programme plays an important role in cancer prevention by identifying potential carcinogenic hazards. However, the terminology used in IARC’s classifications and Monographs can confuse the public, health professionals, and policymakers. Terms like “carcinogenic to humans” imply causation, although classifications only indicate increased risk under certain conditions. For example, the lifetime incidence of mesothelioma among firefighters is approximately 14 in 10,000, compared to 7 in 10,000 in the general population. Despite doubling the risk, occupational exposure as a firefighter does not cause this type of cancer in 9,986 out of 10,000 firefighters. However, the IARC concludes that “occupational exposure as a firefighter causes mesothelioma” (IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Occupational Exposure as a Firefighter. Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addition, the lack of essential information about dosage and context in the IARC carcinogen lists can lead to agents with health benefits under certain conditions (e.g., solar radiation, red meat consumption, approved drugs) being perceived as universally harmful, discouraging beneficial exposures, behaviors, or treatments. Here, I propose renaming the groups of agents classified by the IARC and adding basic labels to specific agents to improve the accuracy and interpretability of the IARC classification lists. These adjustments do not interfere with the IARC’s objective of identifying potential hazards, are easy to implement, and enhance accuracy and clarity, providing stronger support to guide cancer prevention strategies.
Therapeutic Education and Pharmacotherapeutic Follow-Up Protocol, a Useful Tool for the Improvement of Patients at Cardiovascular Risk in Community Pharmacies
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-20) Buenavida Jurado, Pilar; Matta Martín, María José de la; Martín Calero, María José; Puerta Vázquez, Rocío de la; Universidad de Sevilla. Departamento de Farmacología
The aim was to determine the influence of a complex intervention based on pharmacotherapeutic follow-up (PTF) and the application of therapeutic education (TE) protocols on the clinical and educational parameters of patients at cardiovascular risk (CVR) attending community pharmacies (CPs). A prospective, longitudinal, randomized, controlled clinical trial was conducted over 6 months in patients from four Spanish CPs, divided into control (CG) and intervention (IG) groups. CG patients received usual pharmacy care and IG patients received a PTF- and TE-based intervention. The sample consisted of 85 elderly patients. After pharmaceutical follow-up of the IG patients, the following results were observed: significant reductions in cardiovascular risk (CVR) (p < 0.005), blood pressure (BP) (p < 0.05), and sedentary lifestyle (p < 0.001), as well as an improved knowledge of CVR and cardiovascular risk factors (CVRFs) (p < 0.001). Target values for BP were achieved in 27.2% of patients and for triglycerides in 12.4% of patients. The PTF of the patients showed that 29.2% did not have the expected response to some treatments, while 25% had untreated pathologies and 10% had adverse reactions. The TE protocols related to the patients’ educational needs, applied individually and in conjunction with the PTF, were able to improve their lifestyle habits, their knowledge of CVR, CVRFs, and pharmacotherapy, and their clinical parameters, and, thus, the level of development of their disease
Cellular and Molecular Evidence of the Synergistic Antitumour Effects of Hydroxytyrosol and Metformin in Prostate Cancer
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-05) Porcel-Pastrana, Francisco; Montero-Hidalgo, Antonio J.; G-García, Miguel E.; Gil-Duque, Ignacio; Prats-Escribano, Antonio; Gahete, Manuel D.; Sarmento-Cabral, André; Luque, Raúl M.; León González, Antonio José; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Córdoba; Junta de Andalucía
Prostate cancer (PCa) is the tumour pathology with the second highest incidence among men worldwide. PCa is strongly influenced by obesity (OB), which increases its aggressiveness. Hence, some metabolic drugs like metformin have emerged as potential anti-tumour agents against several endocrine-related cancers. Likewise, a high adherence to the Mediterranean diet has been associated with lower rates of OB and a reduction in PCa aggressiveness since this diet contains phenolic bioactive compounds such as hydroxytyrosol (HT) that is mainly present in extra virgin olive oil. Thus, we decided to analyse the therapeutic potential of the combination of HT + metformin in different PCa cell models. Specifically, combinations of different doses of HT and metformin were evaluated by analysing the proliferation rate of LNCaP, 22Rv1, DU-145, and PC−3 cells using the SynergicFinder method. The results revealed a synergistic effect of HT + metformin in significantly reducing proliferation, especially in LNCaP cells. This anti-tumour effect of HT + metformin was also confirmed in migration and tumoursphere formation assays in LNCaP. The effects on the cell cycle and apoptosis were also assessed by flow-cytometry, and a cycle arrest in the G1 phase and an increase in late apoptosis were observed with the combination of HT + metformin. The phosphorylation levels of critical components of different oncogenic pathways were measured which revealed that the combination of HT + metformin significantly reduced the activity of multiple components of the MAPK, AKT, and TGF-β pathways. Overall, the combination of HT + metformin might represent a new therapeutic avenue for the management of PCa patients, an observation that certainly warrants further investigation through a well-designed clinical trial.
Spanish Society of Hospital Pharmacy position paper on biosimilar medicines
(Sociedad Española de Farmacia Hospitalaria, 2018) Martínez López de Castro. Noemí; Matilla Fernández, María Belén; Fraga Fuentes, María Dolores; Mangues Bafalluy, Irene; Asensi Díez, Rocío; Cajaraville Ordonana, Gerardo; Morillo Verdugo, Ramón Alejandro; Pérez Encinas, Montserrat; Universidad de Sevilla. Departamento de Farmacología
Biological medicines nowadays have a great impact, as they offer treatment for diverse diseases and suppose a high cost for health system. Biosimilar medicines contain a version of an active substance already authorized as an original biotechnological medicine, whose patent has expired, and they comply with the guidelines published by the European Medicines Agency. These guidelines, where biosimilarity criteria are established, guarantee comparability between biosimilar product and reference one. Biosimilars’ authorization is carried out through a centralized procedure based on clinical, non-clinical and quality studies. These studies allow the extrapolation of indications, frequently, without carrying out additional analyses. In several European countries, switching between original and biosimilar medicine is considered safe. In Spain, Pharmacy and Therapeutic Committee of hospitals, as consensus bodies among health professionals, are the most suitable bodies to establish the interchangeability criteria in each center. Biosimilar drugs contribute to sustainability and to improvement of the accessibility to medicines. Faced with this situation, Spanish Society of Hospital Pharmacy considers interesting to express its position about biosimilar medicines’ strategies. Spanish Society of Hospital Pharmacy, in September 2015, published an information note about biosimilar medicines, in which its role as medicines similar in quality, safety and efficacy to the originals, but at lower cost, was highlighted. Likewise, it was stressed the role of hospital pharmacists within the Pharmacy and Therapeutic Committee of hospitals, where their knowledge for the selection, evaluation and use of medicines could be useful, in coordination and permanent collaboration with other units or clinical services of hospitals.
Evaluación de la experiencia del paciente VIH+ con la atención farmacéutica basada en la metodología CMO
(Sociedad Española de Farmacia Hospitalaria, 2018) Gracia Cantillana Suárez, María de; Manzano García, Mercedes; Aguas Robustillo-Cortés, María de las; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Objetivo: Evaluar la experiencia de pacientes VIH+ con la atención farmacéutica basada en la metodología capacidad-motivación-oportunidad. Método: Estudio transversal, unicéntrico, que incluyó pacientes VIH+ que fueron atendidos en noviembre de 2016 y a los cuales se aplicó el cuestionario validado IEXPAC. Este permite conocer la experiencia de pacientes crónicos sobre la atención sanitaria que reciben. Resultados: Se incluyeron 91 pacientes. La puntuación media global obtenida fue: 9,7 ± 0,3. Los ítems que obtuvieron puntuaciones más elevadas fueron: respetan mi estilo de vida (9,9 ± 0,5); se coordinan para ofrecerme una buena atención (9,9 ± 0,5); me ayudan a seguir el tratamiento (9,9 ± 0,4); se aseguran de que tomo la medicación (9,9 ± 0,4); se preocupan por mi bienestar (9,9 ± 0,4). Los puntos con posibilidades de mejora incluyeron: se preocupan por mí al llegar a casa tras el ingreso hospitalario (8,7 ± 1,2). Conclusiones: La evaluación de la atención farmacéutica basada en el modelo capacidad-motivación-oportunidad cumple un alto nivel en cada punto de interacción identificado.

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