Updated antimicrobial dosing recommendations for obese patients.

The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.

Towards Precision Medicine in Clinical Practice: Alinity C vs. UHPLC-MS/MS in Plasma Aripiprazole Determination.

Therapeutic drug monitoring improves the benefit-risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is considered the gold-standard method for measuring plasma drug concentrations; however, the Alinity C system has emerged as a promising alternative. This is the first study aimed at comparing UHPLC-MS/MS versus Alinity C in measuring plasma concentrations of aripiprazole and dehydroaripiprazole. A total of 86 plasma samples were analyzed. The active moiety of aripiprazole was measured in 60 samples using both systems and 26 samples were analyzed twice using Alinity C with an intermediate period of 6 months to assess its reproducibility. Spearman's correlation revealed a good association between the two assays (rs = 0.96) and no significance differences were found by McNemar's test when classifying samples between infra-, supra- and therapeutic ranges. Passing-Bablock regression showed a good correlation among methods (rs = 0.93) and a slope of 1.12 indicating a slight tendency of Alinity C to measure higher values than UHPLC-MS/MS. In addition, a good intra-method correlation across the two sequential analyses with Alinity C was obtained (rs = 0.99). Nonetheless, clinical decisions could be different in 15% of the cases depending on the chosen method. No differences were found in active moiety determination by Alinity C depending on the concentration of aripiprazole and dehydroaripiprazole of the samples.

Towards precision medicine of long-acting aripiprazole through population pharmacokinetic modelling.

Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Ampicillin Stability in a Portable Elastomeric Infusion Pump: A Step Forward in Outpatient Parenteral Antimicrobial Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion pumps is postulated as a very promising solution to treat complicated infections, such as endocarditis or osteomyelitis, that require patients to stay in hospital during extended periods of time, thus reducing their quality of life and increasing the risk of complications. However, stability studies of drugs in elastomeric devices are scarce, which limits their use in OPAT. Therefore, we evaluated the stability of ampicillin in sodium chloride 0.9% at two different concentrations, 50 and 15 mg/mL, in an elastomeric infusion pump when stored in the refrigerator and subsequently in real-life conditions at two different temperatures, 25 and 32 °C, with and without the use of a cooling device. The 15 mg/mL ampicillin is stable for up to 72 h under refrigeration, allowing subsequent dosing at 25 °C for 24 h with and without a cooling device, but at 32 °C its concentration drops below 90% after 8 h. In contrast, 50 mg/mL ampicillin only remains stable for the first 24 h under refrigeration, and subsequent administration at room temperature is not possible, even with the use of a cooling system. Our data support that 15 mg/mL AMP is suitable for use in OPAT if the volume and rate of infusion are tailored to the dosage needs of antimicrobial treatments.

Efficacy and Safety of Inhaled Ethanol in Early-Stage SARS-CoV-2 Infection in Older Adults: A Phase II Randomized Clinical Trial.

BACKGROUND: Inhaled ethanol in the early stages of SARS-CoV-2 infection may reduce the viral load, decreasing progression and improving prognosis. The ALCOVID-19 trial was designed to study the efficacy and safety of inhaled ethanol in older adults at initial phases of infection. METHODS: Randomized, triple-blind, placebo-controlled phase II clinical trial. Experimental group (n = 38) inhaled 65° ethanol through an oxygen flow, while in the control group (n = 37), water for injection was used. General endpoint was to evaluate disease progression according to the modified World Health Organization (WHO) Clinical Progression Scale. Specific effectiveness endpoints were body temperature, oxygen saturation, viral load assessed by cycle threshold (Ct) on real-time polymerase chain reaction (RT-PCR), analytical biomarkers and use of antibiotics or corticosteroids. Specific safety outcomes were the absence of ethanol in plasma, electrographic, analytical, or respiratory alterations. RESULTS: In the intention-to-treat population, no differences were found regarding disease progression. Mean Ct values increased over time in both groups, being numerically higher in the ethanol group, reaching a value above 33 only in the ethanol group on day 14, a value above which patients are considered non-infective. No differences were found in the other specific effectiveness endpoints. Inhaled ethanol was proven to be safe as no plasma ethanol was detected, and there were no electrocardiographic, analytical, or respiratory alterations. CONCLUSIONS: The efficacy of inhaled ethanol in terms of the progression of SARS-CoV-2 infection was not demonstrated in the present trial. However, it is positioned as a safe treatment for elderly patients with early-stage COVID-19.

TELEA-Farmacia: Pharmaceutical care by Telepharmacy to oncology patients from a hospital pharmacy service.

OBJECTIVE: To describe the implementation of a pilot Telepharmacy project (TELEA-Farmacia) in adult patients with cancer, analyze the results obtained, and identify opportunities for improvement, from a hospital  pharmacy service. METHOD: Between October and December 2021, oncology patients, collecting  their oral antineoplastic drugs at the Unit of Oncology Pharmacy of the hospital pharmacy service were stratified using the MAPEX model. Oncology patients  candidates for inclusion in the TELEA-Farmacia project included "medium-high  priority" hospital pharmacy patients, along with oncology patients who,  according to pharmacist's opinion, could benefit from Telepharmacy. On a  weekly basis, oncology patients recorded on the TELEA platform their biological  measurements and completed the questionnaires on medication  adherence and pain. Questionnaires on quality of life were completed on a  monthly basis. To score health indicators, oncology patients accessed TELEA  through the SERGAS-MOBIL app or a web browser. Follow-up of health  indicators was performed by the Unit of Oncology Pharmacy of the hospital  pharmacy service. RESULTS: The study sample included 29 oncology patients (48% were male)  with a mean age of 59 years (44-75). According to the stratification model,  31% were low-priority patients, 62% had medium-priority, and 7%  had high  priority. The digital gap in patients with advanced ages was the main obstacle  to inclusion. Reports were monitored daily, and a total of 364 responses were  received. In the presence of alarming reports and/or out-of-range values,  active monitoring and/or telephonic follow-up were initiated. Pharmaceutical  care was adapted to the health problem detected according to individual  patient needs. CONCLUSIONS: The Telemedicine pilot project TELEA-Farmacia made it possible  to test TELEA in patients with cancer in a real-life context. TELEA facilitated  continuous follow-up, early detection of drug-related problems, and the  identification of new needs and improvement points. To such purpose, clinical  oncology pharmacists combined face-to-face consults with patient stratification  and remote follow-up. This study demonstrated that new  stratification models are necessary in hospital pharmacy services to identify  patients with technology skills who can benefit from using Telemedicine tools  as TELEA.

OBJETIVO: Describir la implantación de un proyecto piloto de Telefarmacia (TELEA-Farmacia) en el paciente oncológico adulto y analizar los resultados recabados, así como identificar las oportunidades de mejora, desde un servicio de farmacia hospitalario.Método: Entre octubre y diciembre de 2021, los pacientes oncológicos a  tratamiento con antineoplásicos orales citados en la consulta de farmacia oncológica del servicio de farmacia de hospital fueron estratificados a  través del modelo MAPEX. Se consideraron susceptibles de inclusión en TELEA- Farmacia a quienes requerían atención farmacéutica con "prioridad media-alta" y a aquellos que, según criterio farmacéutico, pudieran beneficiarse de la herramienta. A través del aplicativo TELEA se programaron semanalmente biomedidas y cuestionarios de adherencia y evaluación del  dolor, y mensualmente un cuestionario de calidad de vida. Accediendo a TELEA  mediante la aplicación móvil SERGAS-MÓBIL o un navegador web, los  pacientes oncológicos respondieron a los indicadores de salud programados, de cuyo seguimiento fue responsable la Unidad de Farmacia Oncológica del  servicio de farmacia de hospital. RESULTADOS: Se incluyeron 29 pacientes oncológicos (48% hombres), con una  media de 59 años (44-75). Un 31% fueron de prioridad baja, 62% media y 7%  alta según el modelo de estratificación, siendo la brecha digital existente  en edades avanzadas el principal impedimento para la inclusión. Se realizó un  seguimiento diario de las notificaciones, recibiéndose un total de 364  respuestas. A partir de las consideradas alarmantes y de los valores fuera de  rango, se procedió al seguimiento activo y/o contacto telefónico,  proporcionando atención farmacéutica adaptada al problema de salud  detectado en función de las necesidades. CONCLUSIONES: El proyecto piloto de Telemedicina TELEA-Farmacia permitió testar la herramienta en pacientes oncológicos en vida real, facilitando el seguimiento continuado, la detección temprana de problemas  relacionados con medicamentos y la identificación de nuevas necesidades y  puntos de mejora para su implantación definitiva en la actividad asistencial.  Para ello, fue necesario compaginar la actividad presencial en consulta con el tiempo requerido para la estratificación y seguimiento telemático. Además, ha evidenciado la necesidad de disponer de nuevos modelos de  estratificación en un servicio de farmacia de hospital para la atención  farmacéutica que contemplen el manejo de las tecnologías por parte de los  pacientes, para identificar así a quienes más se puedan beneficiar de la  herramienta de Telemedicina TELEA.

Stability of insulin eye drops in the treatment of refractory corneal ulcers.

OBJECTIVE: To determine and compare the physicochemical and microbiological stability of two 25 IU/mL insulin eye drop formulations made with normal saline and a balanced salt solution, respectively, stored for 120 days under various conditions. METHOD: Eye drops were compounded in triplicate with 100 IU/mL Actrapid®  insulin and either normal saline or a balanced salt solution as vehicles, and  they were stored alternatively at room temperature (25 °C), in a refrigerator  (2-8 °C) or in a freezer (-20 °C) for 120 days. Insulin concentrations were  determined by ultra-high resolution liquid chromatography, and osmolality and  pH values were measured at days 0, 3, 7, 15, 30, 60, 90 and 120. Likewise,  samples were extracted for microbiological studies on days 0, 30, 60, 90 and  120. RESULTS: The formulation made with normal saline maintained insulin concentrations above 90% of the baseline level after 120 days across all  temperature conditions. In the case of the balanced salt solution- based eye drops, insulin concentration when stored at room temperature or in the freezer remained stable after 120 days, although insulin concentration when stored in the refrigerator fell below 90% on day 90 of the  study. Osmolality and pH values remained constant in both formulations and across all storage conditions. No microbiological growth was observed in any of the samples. CONCLUSIONS: 25 IU/mL insulin eye drops made with normal saline remain  stable for 120 days whether they are stored at room temperature, in a  refrigerator or in a freezer, provided that they are protected from light. When  made with a balanced salt solution, they remain stable for 120 days at room  temperature and in a freezer, their shelf life being reduced to 90 days in the  case of storage in a refrigerator.

OBJETIVO: Determinar y comparar la estabilidad físico-química y microbiológica de dos colirios de insulina 25 UI/ml elaborados con suero fisiológico o balanced salt solution bajo diferentes condiciones de  conservación durante 120 días.Método: Los colirios se elaboraron por triplicado con insulina Actrapid® 100  Ul/ml y balanced salt solution o suero fisiológico como vehículo, y fueron  conservados a temperatura ambiente (25 °C), en nevera (2-8 °C) o congelador  (­20 °C) durante 120 días. Se determinó la concentración de  insulina mediante cromatografía liquida de ultra alta resolución, la osmolalidad  y el pH a días 0, 3, 7, 15, 30, 60, 90 y 120. Asimismo, se extrajeron muestras  para estudios microbiológicos en los días 0, 15, 30, 60, 90 y 120. RESULTADOS: La formulación elaborada con suero fisiológico mantuvo la  concentración de insulina por encima del 90% con respecto a la inicial tras 120  días de estudio en todas las condiciones de temperatura. En el caso del  colirio elaborado con balanced salt solution, la concentración se mantuvo  estable en ambiente y congelador tras 120 días, aunque en nevera descendió  por debajo del 90% a día 90 de estudio. Los valores de osmolalidad y pH se  mantuvieron constantes en ambas formulaciones y condiciones de  conservación. No se observó crecimiento microbiológico en ninguna de las  muestras retiradas. CONCLUSIONES: El colirio de insulina 25 UI/ml elaborado con suero fisiológico  es estable 120 días, conservado tanto a temperatura ambiente como en nevera  o congelador, protegido de la luz. Con balanced salt solution  permanece estable 120 días a temperatura ambiente y congelador, reduciéndose el periodo de validez a 90 días en el caso de la conservación en nevera.

TELEA-Farmacia: Atención farmacéutica mediante Telefarmacia a pacientes oncológicos desde un servicio de farmacia hospitalaria / TELEA-Farmacia: Pharmaceutical care by Telepharmacy to oncology patients from a hospital pharmacy service

Objetivo: Describir la implantación de un proyecto piloto de Telefarmacia (TELEA-Farmacia) en el paciente oncológico adulto y analizar losresultados recabados, así como identificar las oportunidades de mejora,desde un servicio de farmacia hospitalario.Método: Entre octubre y diciembre de 2021, los pacientes oncológicosa tratamiento con antineoplásicos orales citados en la consulta de farmaciaoncológica del servicio de farmacia de hospital fueron estratificados a travésdel modelo MAPEX. Se consideraron susceptibles de inclusión en TELEA-Farmacia a quienes requerían atención farmacéutica con “prioridad media-alta”y a aquellos que, según criterio farmacéutico, pudieran beneficiarse de laherramienta. A través del aplicativo TELEA se programaron semanalmentebiomedidas y cuestionarios de adherencia y evaluación del dolor, y mensualmente un cuestionario de calidad de vida. Accediendo a TELEA mediantela aplicación móvil SERGAS-MÓBIL o un navegador web, los pacientesoncológicos respondieron a los indicadores de salud programados, de cuyoseguimiento fue responsable la Unidad de Farmacia Oncológica del serviciode farmacia de hospital.Resultados: Se incluyeron 29 pacientes oncológicos (48% hombres),con una media de 59 años (44-75). Un 31% fueron de prioridad baja,62% media y 7% alta según el modelo de estratificación, siendo la brecha. digital existente en edades avanzadas el principal impedimento para lainclusión. Se realizó un seguimiento diario de las notificaciones, recibiéndose un total de 364 respuestas. A partir de las consideradas alarmantesy de los valores fuera de rango, se procedió al seguimiento activo y/ocontacto telefónico, proporcionando atención farmacéutica adaptada alproblema de salud detectado en función de las necesidades. (AU)

Objective: To describe the implementation of a pilot Telepharmacy project (TELEA-Farmacia) in adult patients with cancer, analyze the resultsobtained, and identify opportunities for improvement, from a hospital pharmacy service.Method: Between October and December 2021, oncology patients,collecting their oral antineoplastic drugs at the Unit of Oncology Pharmacy of the hospital pharmacy service were stratified using the MAPEXmodel. Oncology patients candidates for inclusion in the TELEA-Farmaciaproject included “medium-high priority” hospital pharmacy patients, alongwith oncology patients who, according to pharmacist’s opinion, couldbenefit from Telepharmacy. On a weekly basis, oncology patients recorded on the TELEA platform their biological measurements and completedthe questionnaires on medication adherence and pain. Questionnaires onquality of life were completed on a monthly basis. To score health indicators, oncology patients accessed TELEA through the SERGAS-MOBIL appor a web browser. Follow-up of health indicators was performed by theUnit of Oncology Pharmacy of the hospital pharmacy service.Results: The study sample included 29 oncology patients (48% weremale) with a mean age of 59 years (44-75). According to the stratificationmodel, 31% were low-priority patients, 62% had medium-priority, and 7%. had high priority. The digital gap in patients with advanced ages was themain obstacle to inclusion. Reports were monitored daily, and a total of364 responses were received. In the presence of alarming reports and/orout-of-range values, active monitoring and/or telephonic follow-up wereinitiated. Pharmaceutical care was adapted to the health problem detected according to individual patient needs. (AU)

Estabilidad del colirio de insulina para el tratamiento de úlceras corneales refractarias / Stability of insulin eye drops in the treatment of refractory corneal ulcers

Objetivo: Determinar y comparar la estabilidad físico-química y microbiológica de dos colirios de insulina 25 UI/ml elaborados con suerofisiológico o balanced salt solution bajo diferentes condiciones de conservación durante 120 días.Método: Los colirios se elaboraron por triplicado con insulina Actrapid®100 Ul/ml y balanced salt solution o suero fisiológico como vehículo, yfueron conservados a temperatura ambiente (25 °C), en nevera (2-8 °C)o congelador (–20 °C) durante 120 días. Se determinó la concentraciónde insulina mediante cromatografía liquida de ultra alta resolución, laosmolalidad y el pH a días 0, 3, 7, 15, 30, 60, 90 y 120. Asimismo, seextrajeron muestras para estudios microbiológicos en los días 0, 15, 30,60, 90 y 120.Resultados: La formulación elaborada con suero fisiológico mantuvola concentración de insulina por encima del 90% con respecto a la inicialtras 120 días de estudio en todas las condiciones de temperatura. En elcaso del colirio elaborado con balanced salt solution, la concentraciónse mantuvo estable en ambiente y congelador tras 120 días, aunque ennevera descendió por debajo del 90% a día 90 de estudio. Los valoresde osmolalidad y pH se mantuvieron constantes en ambas formulacionesy condiciones de conservación. No se observó crecimiento microbiológico en ninguna de las muestras retiradas.Conclusiones: El colirio de insulina 25 UI/ml elaborado con suerofisiológico es estable 120 días, conservado tanto a temperatura ambientecomo en nevera o congelador, protegido de la luz. Con balanced saltsolution permanece estable 120 días a temperatura ambiente y congelador, reduciéndose el periodo de validez a 90 días en el caso de laconservación en nevera. (AU)

Objective: To determine and compare the physicochemical and microbiological stability of two 25 IU/mL insulin eye drop formulations madewith normal saline and a balanced salt solution, respectively, stored for120 days under various conditions.Method: Eye drops were compounded in triplicate with 100 IU/mLActrapid® insulin and either normal saline or a balanced salt solution asvehicles, and they were stored alternatively at room temperature (25 °C),in a refrigerator (2-8 °C) or in a freezer (–20 °C) for 120 days. Insulinconcentrations were determined by ultra-high resolution liquid chromatography, and osmolality and pH values were measured at days 0, 3, 7,15, 30, 60, 90 and 120. Likewise, samples were extracted for microbiological studies on days 0, 30, 60, 90 and 120.Results: The formulation made with normal saline maintained insulinconcentrations above 90% of the baseline level after 120 days acrossall temperature conditions. In the case of the balanced salt solution-basedeye drops, insulin concentration when stored at room temperature or inthe freezer remained stable after 120 days, although insulin concentrationwhen stored in the refrigerator fell below 90% on day 90 of the study.Osmolality and pH values remained constant in both formulations andacross all storage conditions. No microbiological growth was observedin any of the samples. Conclusions: 25 IU/mL insulin eye drops made with normal salineremain stable for 120 days whether they are stored at room temperature,in a refrigerator or in a freezer, provided that they are protected fromlight. When made with a balanced salt solution, they remain stable for120 days at room temperature and in a freezer, their shelf life being reduced to 90 days in the case of storage in a refrigerator. (AU)

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at -20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at -20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

A Review of Population Pharmacokinetic Analyses of Linezolid.

In recent years, many studies on population pharmacokinetics of linezolid have been conducted. This comprehensive review aimed to summarize population pharmacokinetic models of linezolid, by focusing on dosage optimization to maximize the probability of attaining a certain pharmacokinetic-pharmacodynamic parameter in special populations. We searched the PubMed and EMBASE databases for population pharmacokinetic analyses of linezolid using a parametric non-linear mixed-effect approach, including both observational and prospective trials. Of the 32 studies, 26 were performed in adults, four in children, and one in both adults and children. High between-subject variability was determined in the majority of the models, which was in line with the variability of linezolid concentrations previously detected in observational studies. Some studies found that patients with renal impairment, hepatic failure, advanced age, or low body weight had higher exposure and adverse reactions rates. In contrast, lower concentrations and therapeutic failure were associated with obese patients, young patients, and patients who had undergone renal replacement techniques. In critically ill patients, the inter-individual and intra-individual variability was even greater, suggesting that this population is at an even higher risk of underexposure and overexposure. Therapeutic drug monitoring may be warranted in a large proportion of patients given that the Monte Carlo simulations demonstrated that the one-size-fits-all labeled dosing of 600 mg every 12 h could lead to toxicity or therapeutic failure for high values of the minimum inhibitory concentration of the target pathogen. Further research on covariates, including renal function, hepatic function, and drug-drug interactions related to P-glycoprotein could help to explain variability and improve linezolid dosing regimens.

Current Situation and Challenges in Vitreous Substitutes.

Vitreo-retinal disorders constitute a significant portion of treatable ocular diseases. These pathologies often require vitreo-retinal surgery and, as a consequence, the use of vitreous substitutes. Nowadays, the vitreous substitutes that are used in clinical practice are mainly divided into gases (air, SF6 , C2 F6 , C3 F8 ) and liquids (perfluorocarbon liquids, silicone oils, and heavy silicone oils). There are specific advantages and drawbacks to each of these, which determine their clinical indications. However, developing the ideal biomaterial for vitreous substitution continues to be one of the most important challenges in ophthalmology, and a multidisciplinary approach is required. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable hydrogels (natural, synthetic, and smart), which also act as medium and long-term internal tamponade agents. This comprehensive review aims to cover the main characteristics and indications for use of the extensive range of vitreous substitutes that are currently used in clinical practice, before going on to describe the hydrogels that have been developed recently and which have emerged as promising biomaterials for vitreous substitution.

Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection.

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.

Regulación de la innovación en formulación magistral oftálmica / Regulating innovation in compounded ophthalmic preparations

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Nuevos sistemas de liberación de fármacos a nivel ocular / New ophthalmic drug delivery systems

Desde hace décadas, la administración tópica oftálmica de fármacos mediante el empleo de colirios ha sido la técnica más empleada para el tratamiento de patologías oculares. El desarrollo de la galénica ha permitido el uso y comercialización de nuevas formulaciones que incrementan el tiempo de residencia en el lugar de acción, como es el caso de las sus-pensiones, emulsiones y pomadas oftálmicas. Recientemente se han desarrollado nuevos sistemas de administración, como es el caso de dispositivos e insertos que proporcionan una cesión sostenida de principio activo. Algunos de estos sistemas ya se encuentran disponibles en el mercado, mientras que otros todavía están en fase de ensayo clínico, como es el caso también de los prometedores sistemas basados en nanoestructuras (nanocápsulas, ciclodextrinas, nanoemulsiones, etc.). De la misma forma, diversas formulaciones y dispositivos han sido desarrollados en el campo de la administración intravítrea, estando disponibles en el mercado euro-peo diversos implantes para el tratamiento de la degeneración macular asociada a la edad (DMAE), el edema macular diabético o infecciones que afectan al segmento posterior. En esta revisión se recogen los desarrollos actualmente implementados y en fase de investigación asociados a las vías de administración oftálmica de fármacos tópicos e intravítreos

For decades, topical ophthalmic drug administration through the use of eye drops has been the most widely used technique for the treatment of eye diseases. The development of galenic formulation has led to the use and commercialization of new formulations, such as suspensions, emulsions, and ophthalmic ointments that increase residence time in the site of action. Recently, new administration systems have been developed, such as devices and inserts that provide the sustained release of active substance. Some of these systems are already available on the market, whereas others are still undergoing clinical trials, such as promising systems based on nanostructures (nanocapsules, cyclodextrins, nanoemulsions, etc.). Similarly, various formulations and devices have been developed in the field of intravitreal administration, with different implants available on the European market for the treatment of age-related macular degeneration (AMD), diabetic macular edema, or infections that affect the posterior segment. This review includes current developments in ophthalmic topical and intravitreal drug administration routes as well as those under investigation