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.
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, C2F6, C3F8) 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.
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.
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).