En el artículo «Guía Clínica Española del Acceso Vascular para Hemodiálisis» (Nefrologia. 2017;37[Supl 1]:1-192) se ha detectado un error en la filiación de la Dra. Isabel Crehuet, siendo la correcta: Hospital Universitario Río Hortega, Valladolid

Complete monoclonal IgG antibodies which are in use in clinical practice share some pharmacological properties resulting in high concentrations in plasma. This fact is reflected in their low volumes of distribution, which can also be correlated with a high molecular weight and water solubility. This feature allows a novel approach to be applied to the dosing schedule for this group of drugs with fixed doses being used instead of the initially developed weight- or body surface-adjusted dosing schedules. In addition, the development of a new formulation containing hyaluronidase allows a subcutaneous route of administration to be used, because hyaluronidase creates a space in the subcutaneous tissue that helps antibody absorption. This method requires higher doses, but has allowed testing the feasibility of administering a fixed dose, with no individual dose adjustments based on weight or body surface. Moreover, loading doses are not needed, because the first dose results, within 3 weeks, in minimum concentrations that are higher than effective concentrations.

El tratamiento de la aspergilosis invasora exige la utilización de algunos fármacos que de forma característica presentan propiedades farmacocinéticas complejas, cuyo conocimiento es imprescindible para alcanzar la máxima eficacia con el mínimo riesgo para el paciente. Las formulaciones lipídicas de anfotericina B son muy distintas en su comportamiento farmacocinético, con concentraciones plasmáticas de la forma liposómica muy elevadas en probable relación con la presencia de colesterol en su estructura. Los azoles presentan un perfil de absorción variable, especialmente en el caso del itraconazol y del posaconazol, este último muy dependiente de múltiples factores. En el caso del voriconazol puede existir variabilidad a este respecto, lo que obliga a considerar la posibilidad de realizar una monitorización de las concentraciones plasmáticas. El objetivo de este artículo es revisar algunos de los aspectos más relevantes de la farmacología de los antifúngicos utilizados en la profilaxis y el tratamiento de la infección aspergilar. Por ello se incluirán los aspectos más relevantes de algunos de los azoles que suelen prescribirse en esta infección (itraconazol, posaconazol y voriconazol) y de las formulaciones de anfotericina B.

The objective of this study was to evaluate ocular tolerance, safety, and effect on intraocular pressure (IOP) of a topically administered small interfering RNA; SYL040012, on healthy volunteers. The study was an open-label, controlled, single-center study comprised of two intervals that enrolled 30 healthy subjects having IOP below 21 mmHg. SYL040012 was administered to one eye as a single dose to six subjects during interval 1. During interval 2 two different doses of SYL040012 were administered to one eye on a daily basis to two separate groups of 12 subjects each, over a period of 7 days. The contralateral eye was evaluated but not administered and served as control for the tolerance study. SYL040012 was well tolerated locally. No local or systemic adverse events related to the product developed in response to any of the doses studied. SYL040012 was not detected in plasma at any time point. Administration of SYL040012 over a period of 7 days reduced IOP values in 15 out of 24 healthy subjects regardless of the dose used. IOP decrease was statistically significant in response to one of the doses tested and responsiveness to SYL040012 seemed to be greater in individuals with higher baseline IOP.

Background: Palonosetron is a potent second generation 5-hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. Patients and Methods: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC(0-24h), t(1/2), and C-max observed with each route of administration by analysis of variance (ANOVA). Results: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng x h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). C-max was lower with SC than with IV route and was reached 15 minutes following SC administration. Conclusions: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.

Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness

The absorption of bilastine after oral administration to healthy subjects was rapid. The absolute oral bioavailability was moderate

Bilastine is a potent inhibitor of the histamine H1 receptor. It was recently approved in 28 countries of the European Union for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. Data from preclinical studies confirmed its selectivity for the histamine H1 receptor over other receptors, and demonstrated antihistaminic and antiallergic properties in vivo. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. Bilastine has demonstrated a good safety profile, without serious adverse effects or antimuscarinic effects in clinical trials. There were no significant changes in laboratory tests, electrocardiograms or vital signs. In clinical studies, oral treatment with bilastine 20 mg once daily improved allergic rhinitis with greater efficacy than placebo and comparable to cetirizine and desloratadine. Bilastine 20 mg was more effective than placebo and equivalent to levocetirizine in chronic urticaria, relieving symptoms, improving quality of life and controlling sleep disorders.

Objectives: The prevention of venous thromboembolism (VTE) is a priority for improved safety in hospitalised patients. Worldwide, there is growing concern over the undersuse of appropriate thromboprophylaxis. Computerised decision support improves the implementation of thromboprophylaxis and reduces inpatient VTE. However, an economic assessment of this approach has not yet been performed. Objectives: To evaluate the economic impact of an electronic alert (e-alert) system to prevent VTE in hospitalised patients over a 4 year period. Patients/methods: All hospitalised patients at a single institution during the first semesters of 2005-2009 (n = 32 280) were included. All cases of VTE developed during hospitalisation were followed and direct costs of diagnosis and management collected. Results: E-alerts achieved a sustained reduction of the incidence of in-hospital VTE, OR 0.50 (95% CI, 0.29-0.84), the impact being especially significant in medical patients, OR 0.44 (95% CI, 0.22-0.86). No increase in prophylaxis-related bleeding was observed. In our setting, the mean direct cost (during hospitalisation and after discharge) of an in-hospital VTE episode is euro7058. Direct costs per single hospitalised patient were reduced after e-alerts from euro21.6 to euro11.8, while the increased use of thromboprophylaxis and the development of e-alerts meant euro3 and euro0.35 per patient, respectively. Thus, the implementation of e-alerts led to a net cost saving of euro6.5 per hospitalised patient. Should all hospitalised patients in Spain be considered, total yearly savings would approach euro30 million. Conclusions: E-alerts are useful and cost-effective tools for thromboprophylaxis strategy in hospitalised patients. Fewer thromboembolic complications and lower costs are achieved by its implementation

La infección fúngica invasora (IFI) en el trasplante de órgano sólido (TOS) se asocia a una importante mortalidad (30-100%) debido a la dificultad que existe para hacer un diagnóstico precoz en estos pacientes y a los relativamente escasos recursos terapéuticos con los que todavía contamos. En los últimos años se han producido múltiples avances en diferentes aspectos de la IFI en la TOS que han sido recogidos detalladamente en esta monografía de la colección "Trasplantes en el siglo XXI" por un importante grupo de prestigiosos autores nacionales en este campo.