Revistas
Revista:
REVISTA IBEROAMERICANA DE MICOLOGIA
ISSN 1130-1406
Vol. 38
N° 2
Año 2021
Págs.52 - 55
Liposomal amphotericin B is a lipid formulation of the antifungal drug amphotericin B with some distinguishing characteristics in its pharmacological behavior that entail some clinical differences of great interest. The significant improvement in the systemic and renal tolerability is one of them. This fact is related to the great stability of the liposome, promoted by its negative charge, the presence of cholesterol and the remarkable thermo-stability of the remaining lipids that compose it. In this situation, amphotericin B seems to be released from the liposome not spontaneously but when the liposome binds to the ergosterol in the fungal cell membrane. For this reason, there is almost no free amphotericin B in plasma or tissues, although it seems that its availability is greater when there is fungal infection. As a consequence, when the pharmacokinetic behavior is studied, the concentration and availability of liposomal amphotericin B are very high, and its volume of distribution is reduced in comparison with the other formulations. (C) 2021 Asociacion Espafiola de Micologla. Published by Elsevier Espafia, S.L.U. All rights reserved.
Autores:
Mensa, J.; Barberan, J. (Autor de correspondencia); Ferrer, R.; et al.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 34
N° 5
Año 2021
Págs.511 - 524
Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.
Revista:
MYCOSES
ISSN 0933-7407
Vol. 64
N° 1
Año 2021
Págs.66 - 77
Background Invasive mould diseases are associated with high morbidity, mortality and economic impact. Its treatment is often started prior to differential pathogen diagnosis. Isavuconazole is approved for treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) when amphotericin-B is not indicated. Objectives To estimate the cost-effectiveness of isavuconazole vs voriconazole for the treatment of adult patients with possible IA prior to differential pathogen diagnosis, in Spain. Methods A decision tree analysis was performed using the Spanish Healthcare System perspective. Among all patients with possible IA, it was considered that 7.81% actually had IM. Costs for laboratory analysis, management of adverse events, hospitalisation and drugs per patient, deaths and long-term effects in life years (LYs) and quality-adjusted LYs (QALYs) were considered. Efficacy data were obtained from clinical trials and utilities from the literature. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results In patients with possible IA and when compared to voricanozole, isavuconazole showed an incremental cost of 4758.53euro, besides an incremental effectiveness of +0.49 LYs and +0.41 QALYs per patient. The Incremental Cost Effectiveness Ratio was 9622.52euro per LY gained and 11,734.79euro per QALY gained. The higher cost of isavuconazole was due to drug acquisition. Main parameters influencing results were mortality, treatment duration and hospitalisation days. The PSA results showed that isavuconazole has a probability of being cost-effective of 67.34%, being dominant in 24.00% of cases. Conclusions Isavuconazole is a cost-effective treatment compared to voriconazole for patients with possible IA for a willingness to pay threshold of 25,000euro per additional QALY.
Revista:
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
ISSN 0378-7966
Vol. 45
N° 2
Año 2020
Págs.265 - 272
Background and Objective Bilastine is a non-sedating H1 antihistamine indicated for the treatment of allergic rhinoconjunctivitis and urticaria. The aim of this trial was to assess the bioequivalence of three novel pediatric oral formulations of bilastine. Methods An open label, randomized, four-treatment-period, four-sequence, crossover, single-center study was conducted in 23 healthy volunteers. Each subject received four single doses of bilastine under fasting conditions: a 10-mg orodispersible tablet (DT1), a 10-mg oral solution (SOL), a 10-mg orodispersible tablet without water (DT2dry), and a 10-mg orodispersible tablet with water (DT2water, reference formulation). Blood samples were collected during 72 h with a washout period of at least 7 days. Bilastine maximum plasma concentration (C-max) and area under the plasma concentration-time curve between 0 to t time (AUC(0-t)) were calculated to assess bioequivalence. Tolerability was evaluated throughout the study. Results The three oral pediatric formulations tested were bioequivalent to the reference formulation as determined by the ratio test/reference of the geometric mean and their 90% confidence intervals (between 0.80 and 1.25) for the C-max, AUC(0-t) and AUC(0-infinity.) Bilastine was well tolerated when administered indistinctly as an orodispersible tablet or as an oral solution. Conclusion The three oral pediatric formulations tested were found to be bioequivalent to the reference formulation. All formulations were well tolerated.
Revista:
JCO GLOBAL ONCOLOGY
ISSN 2687-8941
Vol. 6
Año 2020
Págs.904 - 905
Revista:
TRIALS
ISSN 1745-6215
Vol. 21
N° 1
Año 2020
Págs.498
Objectives: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment. The secondary objectives are: 1.To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab at day 7 post treatment.2.To assess the efficacy of ivermectin to improve symptom progression in treated patients.3.To assess the proportion of seroconversions in treated patients at day 21.4.To assess the safety of ivermectin at the proposed dose.5.To determine the magnitude of immune response against SARS-CoV-2.6.To assess the early kinetics of immunity against SARS-CoV-2.
Trial design: SAINT is a single centre, double-blind, randomized, placebo-controlled, superiority trial with two parallel arms. Participants will be randomized to receive a single dose of 400 ¿g/kg ivermectin or placebo, and the number of patients in the treatment and placebo groups will be the same (1:1 ratio).
Participants: The population for the study will be patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, with non-severe COVID-19 disease, and no risk factors for progression to severity. Vulnerable populations such as pregnant women, minors (i.e.; under 18 years old), and seniors (i.e.; over 60 years old) will be excluded. Inclusion criteria 1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra (CUN) with a positive SARS-CoV-2 PCR. 2. Residents of the Pamplona basin ("Cuenca de Pamplona"). 3. The patient must be between the ages of 18 and 60 years of age. 4. Negative pregnancy test for women of child bearing age*. 5. The patient or his/her representative, has given informed consent to participate in the study. 6. The patient should, in the PI's opinion, be able to comply with all the requirements of the clinical trial (including home follow up during isolation). Exclusion criteria 1. Known history of ivermectin allergy. 2. Hypersensitivity to any component of ivermectin. 3. COVID-19 pneumonia. Diagnosed by the attending physician.Identified in a chest X-ray. 4. Fever or cough present for more than 48 hours. 5. Positive IgG against SARS-CoV-2 by rapid diagnostic test. 6. Age under 18 or over 60 years. 7. The following co-morbidities (or any other disease that might interfere with the study in the eyes of the PI): Immunosuppression.Chronic Obstructive Pulmonary Disease.Diabetes.Hypertension.Obesity.Acute or chronic renal failure.History of coronary disease.History of cerebrovascular disease.Current neoplasm. 8. Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan). 9. Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin. *Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at least one month afterwards. A woman is considered to not have childbearing capacity if she is post-menopausal (minimum of 2 years without menstruation) or has undergone surgical sterilization (at least one month before the study). The trial is currently planned at a single center, Clínica Universidad de Navarra, in Navarra (Spain), and the immunology samples will be analyzed at the Barcelona Institute for Global Health (ISGlobal), in Barcelona (Spain). Participants will be recruited by the investigators at the emergency room and/or COVID-19 area of the CUN. They will remain in the trial for a period of 28 days at their homes since they will be patients with mild disease. In the interest of public health and to contain transmission of infection, follow-up visits will be conducted in the participant's home by a clinical trial team comprising nursing and medical members. Home visits will assess clinical and laboratory parameters of the patients.
Intervention and comparator: Ivermectin will be administered to the treatment group at a 400¿g/Kg dose (included in the EU approved label of Stromectol and Scabioral). The control group will receive placebo. There is no current data on the efficacy of ivermectin against the virus in vivo, therefore the use of placebo in the control group is ethically justified.
Main outcomes: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1.Mean viral load as determined by PCR cycle threshold (Ct) at baseline and on days 4, 7, 14, and 21.2.Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial.3.Proportion of patients with seroconversion at day 21.4.Proportion of drug-related adverse events during the trial.5.Median levels of IgG, IgM, IgA measured by Luminex, frequencies of innate and SARS-CoV-2-specific T cells assessed by flow cytometry, median levels of inflammatory and activation markers measured by Luminex and transcriptomics.6.Median kinetics of IgG, IgM, IgA levels during the trial, until day 28.
Randomisation: Eligible patients will be allocated in a 1:1 ratio using a randomization list generated by the trial statistician using blocks of four to ensure balance between the groups. A study identification code with the format "SAINT-##" (##: from 01 to 24) will be generated using a sequence of random numbers so that the randomization number does not match the subject identifier. The sequence and code used will be kept in an encrypted file accessible only to the trial statistician. A physical copy will be kept in a locked cabinet at the CUN, accessible only to the person administering the drug who will not enrol or attend to patient care. A separate set of 24 envelopes for emergency unblinding will be kept in the study file.
Blinding (masking): The clinical trial team and the patients will be blinded. The placebo will not be visibly identical, but it will be administered by staff not involved in the clinical care or participant follow up.
Numbers to be randomised (sample size): The sample size is 24 patients: 12 participants will be randomised to the treatment group and 12 participants to the control group.
Trial status: Current protocol version: 1.0 dated 16 of April 2020. Recruitment is envisioned to begin by May 14th and end by June 14th.
Trial registration: EudraCT number: 2020-001474-29, registered April 1st. Clinicaltrials.gov: submitted, pending number FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 32
N° Suppl. 3
Año 2019
Págs.11 - 16
Ceftobiprole shows many similar pharmacokinetic properties to other cephalosporins, except for not being orally bioactive, and that it is administered by IV infusion as the prodrug ceftobiprole medocaril, which is subsequently hydrolyzed in the blood into the active molecule. Distribution focus in extracellular fluid and active antibiotic concentration has been proven in different corporal tissues using dosing regimen of 500 mg intravenous infusion over 2 h every 8 h. Ceftobiprole is eliminated exclusively into the urine, thus the reason why dose adjustment is required for patients with moderate or severe renal impairment, or increased creatinine clearance. However, there is no need for dose adjustments related with other comorbidities and patients' conditions such as age, body weight. Although considering distribution features, molecular weight and dose fraction, increase dosing regimen might be necessary in patients using renal replacement therapy. The half-life of ceftobiprole is more than 3 h, allowing to easily reach optimal PK/PD parameters with the infusion time of 2 h, using the usual dosing regimen.
Revista:
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
ISSN 1201-9712
Vol. 86
Año 2019
Págs.142 - 146
OBJECTIVE: To describe the pharmacokinetic (PK) profile of anidulafungin and to evaluate its concentration in the peritoneal fluid (PF) of patients suspected of suffering from peritoneal infection undergoing abdominal surgery, in order to ensure that therapeutic levels are achieved within the peritoneal cavity.
METHODS: A descriptive, open, prospective, observational, multicentre and non-interventional study was performed. Anidulafungin was used at conventional doses. Blood and PF samples were obtained on day 2 of treatment or on any of the following days.
RESULTS: A total of 31 patients in a serious clinical condition, as demonstrated by high mean clinical severity scale scores (APACHE II and SOFA scores), were included in the study. The mean area under the curve (AUC) in PF was 30% (31±19%) of that determined in the plasma and the maximum concentration (Cmax) reached in PF (mg/l) was close to 1 (0.9±0.5). No adverse effects were observed in any of the 31 patients.
CONCLUSIONS: Anidulafungin at conventional doses reaches PF concentrations that exceed the minimum inhibitory concentration of the usual Candida spp, which explains the proven efficacy of this echinocandin in the treatment of Candida peritonitis in critically ill patients.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 32
N° Supl. 2
Año 2019
Págs.35 - 37
In the past, the dose of an antibiotic was chosen, always from among those that were well tolerated, by considering those with the ability to exceed the MIC of bacteria in plasma. This approach, which has still not widely changed, is contrasted with the pharmacokinetic and pharmacodynamic (PK/PD) relationships, which indicate that the efficacy of antibiotics is directly related to parameters that relate the sequence of concentrations over time with a parameter of the MIC effect in vitro. Until now, three types of PK/PD relationships have been established for antibiotics: the inhibitory coefficient (Cmax/MIC), the efficacy time (T>CMI) and the relationship between the exposure of the drug and the MIC (AUC/MIC)
Autores:
Mensa, J. (Autor de correspondencia); Barberan, J.; Soriano, A.; et al.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 31
N° 1
Año 2018
Págs.78 - 100
Pseudomonas aeruginosa is characterized by a notable intrinsic resistance to antibiotics, mainly mediated by the expression of inducible chromosomic beta-lactamases and the production of constitutive or inducible efflux pumps. Apart from this intrinsic resistance, P. aeruginosa possess an extraordinary ability to develop resistance to nearly all available antimicrobials through selection of mutations. The progressive increase in resistance rates in P. aeruginosa has led to the emergence of strains which, based on their degree of resistance to common antibiotics, have been defined as multidrug resistant, extended-resistant and panresistant strains. These strains are increasingly disseminated worldwide, progressively complicating the treatment of P. aeruginosa infections. In this scenario, the objective of the present guidelines was to review and update published evidence for the treatment of patients with acute, invasive and severe infections caused by P. aeruginosa. To this end, mechanisms of intrinsic resistance, factors favoring development of resistance during antibiotic exposure, prevalence of resistance in Spain, classical and recently appeared new antibiotics active against P. aeruginosa, pharmacodynamic principles predicting efficacy, clinical experience with monotherapy and combination therapy, and principles for antibiotic treatment were reviewed to elaborate recommendations by the panel of experts for empirical and directed treatment of P. aeruginosa invasive infections.
Revista:
REVISTA DE LA SOCIEDAD ESPAÑOLA DEL DOLOR
ISSN 1134-8046
Vol. 25
N° 4
Año 2018
Págs.222-227
Revista:
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY & PHARMACOTHERAPY
ISSN 2456-3501
Vol. 3
Año 2018
Revista:
NEFROLOGIA
ISSN 0211-6995
Vol. 39
N° 1
Año 2018
Págs.1 - 2
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
Revista:
REVISTA IBEROAMERICANA DE MICOLOGIA
ISSN 1130-1406
Vol. 35
N° 4
Año 2018
Págs.186 - 191
Isavuconazole is a new azole, structurally related to fluconazole and voriconazole, that presents a very high oral absorption with no first-pass effect which is not interfered by the presence of food, gastric pH modifications, or mucositis. Its distribution volume is very high, probably also to cerebrospinal fluid, in spite of the fact that it circulates highly bound to plasma proteins. It is extensively metabolized through the CYP3A4 isoenzyme. Due to this reason, it is recommended to avoid co-administration with strong CYP3A4 inducers. In addition, isavuconazole may inhibit CYP3A4. Moreover, it may induce CYP2B6 and Pglycoprotein. Interestingly, this inhibitory activity seems to be lower compared to other azoles. Therefore, the management of any interaction with other medicines is easier, which is probably the most important advantage of this antifungal. (C) 2018 Asociacion Espanola de Micologia. Published by Elsevier Espana, S.L.U. All rights reserved.
Revista:
CLINICOECONOMICS AND OUTCOME RESEARCH
ISSN 1178-6981
Vol. 9
Año 2017
Págs.39 - 47
OBJECTIVE:
According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI) with VOR monotherapy for invasive aspergillosis (IA) in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System.
METHODS:
An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG) for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were obtained from clinical trial data. The costs (in 2015 euros [€]) of the drugs and the adverse event-related costs were obtained from Spanish sources. A Tornado plot and a Monte Carlo simulation (1,000 iterations) were used to assess uncertainty of all model variables.
RESULTS:
According to the deterministic analysis, for each patient treated with VOR+ANI compared with VOR monotherapy, there would be a total of 0.348 LYG (2.529 vs 2.181 years, respectively) at an incremental cost of €5,493 (€17,902 vs €12,409, respectively). Consequently, the additional cost per LYG with VOR+ANI compared with VOR would be €15,785. Deterministic sensitivity analyses confirmed the robustness of these findings. In the probabilistic analysis, the cost per LYG with VOR+ANI was €15,774 (95% confidence interval: €15,763-16,692). The probability of VOR+ANI being cost-effective compared with VOR was estimated at 82.5% and 91.9%, based on local cost-effectiveness thresholds of €30,000 and €45,000, respectively.
CONCLUSION:
According to the present economic study, combination therapy with VOR+ANI is cost-effective as primary therapy of IA in galactomannan-positive patients in Spain who have hematologic disease or hematopoietic stem cell transplant, compared with VOR monotherapy.
Revista:
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA
ISSN 0213-005X
Vol. 35
N° Suppl 1
Año 2017
Págs.22 - 27
Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously. It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high. Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration. Dalbavancin is eliminated slowly, as shown by its clearance value and its terminal elimination half-life, which exceeds 300 hours. This means that adequate concentrations of the drug remain in plasma and tissues for a prolonged period and explains the dosing regimen: a first dose of 1g followed 7 days later by a 500mg dose. The pharmacokinetics are linear and show little intra- and interindividual variability. There are no pharmacokinetic interactions. Dose adjustment is not required for patients with mild or moderate renal insufficiency (creatinine clearance ≥ 30 to 79ml/min). Dosage adjustment is not required in patients regularly receiving elective haemodialysis (3 times/week) and the drug can be administered without consideration of haemodialysis times. In patients with chronic renal insufficiency, whose creatinine clearance is < 30ml/min and who are not regularly receiving elective haemodialysis,
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 29
N° 1
Año 2016
Págs.15 - 24
Introducción.
Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica.
Material y métodos.
Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación.
Resultados.
La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico.
Conclusiones.
Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica.
Revista:
ACTAS ESPAÑOLAS DE PSIQUIATRIA
ISSN 1139-9287
Vol. 44
N° 1
Año 2016
Págs.20 - 29
BACKGROUND:
Metabolic syndrome (MS) and cardiovascular risk factors (CRF) have been associated with patients with schizophrenia. The main objective is to assess the evolution of CRF and prevalence of MS for 12 months in a cohort of overweight patients diagnosed with schizophrenia schizophreniform disorder or schizoaffective disorder in which the recommendations for the assessment and control of metabolic and cardiovascular risk were applied.
METHODS:
The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, observational, prospective, open-label, multicentre, naturalistic study including 109 community mental health clinics of Spain. The study included a total of 403 patients, of whom we could collect all variables related to CRF and MS in 366 patients. Of these 366 patients, 286 completed the follow-up, (baseline, months 3, 6 and 12) where they underwent a complete physical examination and a blood test (glucose, cholesterol and triglycerides), they were asked about their health-related habits (smoking, diet and exercise) and they were given a series of recommendations to prevent cardiovascular risk and MS.
RESULTS:
A total of 403 patients were included, 63% men, mean age (mean; (SD)) 40.5 (10.5) years. After 12 months, the study showed statistically significant decrease in weight (p<0.0001), waist circumference (p<0.0001), BMI (p<0.0001), blood glucose (p=0.0034), total cholesterol (p<0.0001), HDL cholesterol (p=0.02), LDL cholesterol (p=0.0023) and triglycerides (p=0.0005). There was a significant reduction in the percentage of smokers (p=0.0057) and in the risk of heart disease at 10 years (p=0.0353).
CONCLUSION:
Overweight patients with schizophrenia who receive appropriate medical care, including CRF monitoring and control of health-related habits experience improvements with regard to most CRFs.
Revista:
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA
ISSN 0365-6691
Vol. 90
N° Supl. 1
Año 2015
Págs.6 - 10
Aflibercept es una proteina de fusion que combina en su estructura quimica, la fraccion constante de cualquier IgG con una fraccion variable construida con partes fundamentales de los receptores del factor de crecimiento del endotelio vascular, por ello es capaz de fijar a diversas isoformas del factor de crecimiento del endotelio vascular y tambien al factor de crecimiento placentario, lo que se ha puesto en relacion con un posible efecto sinergico en la eficacia. La afinidad es mayor que la que presentan ranibizumab y bevacizumab. Ademas produce un efecto antiinflamatorio intraocular.
La administracion por via intravitrea cursa con la presencia de trazos del farmaco en el plasma del paciente; de hecho, las concentraciones son tan reducidas que la presencia de efectos adversos sistemicos, incluida la hipertension arterial, es practicamente nula. Una semivida de eliminacion intraocular prolongada unida a la afinidad elevada supone que sea posible la utilizacion en pautas posologicas comodas, ya que tras una inyeccion mensual para las 3 primeras dosis se aumenta el intervalo a una inyeccion cada 2 meses, que tras los primeros 12 meses puede vincularse a los resultados visuales y anatomicos.
Revista:
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
ISSN 0269-4727
Vol. 40
N° 5
Año 2015
Págs.601 - 603
What is known and objectiveInvasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system.
Case summaryWe present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment.
What is new and conclusionThis is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 28
N° 6
Año 2015
Págs.275 - 281
This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.
Revista:
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
ISSN 1078-1552
Vol. 21
N° 5
Año 2015
Págs.370 - 376
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.
Revista:
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
ISSN 0305-7453
Vol. 69
N° 6
Año 2014
Págs.1620-23
The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.
Autores:
Len, O.; Montejo, M.; Cervera, C.; et al.
Revista:
TRANSPLANT INFECTIOUS DISEASE
ISSN 1398-2273
Vol. 16
N° 4
Año 2014
Págs.532 - 538
Introduction Infections caused by resistant gram-positive cocci (GPC), especially to glycopeptides, are difficult to treat in solid organ transplant (SOT) recipients as a result of lower effectiveness and high rates of renal impairment. The aim of this study was to evaluate the use of daptomycin in this population. Methods Over a 2-year period (March 2008-2010) in 9 Spanish centers, we enrolled all consecutive recipients who received daptomycin to treat GPC infection. The study included 43 patients, mainly liver and kidney transplant recipients. Results The most frequent infections were catheter-related bacteremia caused by coagulase-negative staphylococci (23.2%), skin infection caused by Staphylococcus aureus (11.5%), and intra-abdominal abscess caused by Enterococcus faecium (20.9%). The daily daptomycin dose was 6mg/kg in 32 patients (74.4%). On day 7 of daptomycin treatment, median estimated area under the curve was 1251g/mL/h. At the end of follow-up, analytical parameters were similar to the values at the start of therapy. No changes were observed in tacrolimus levels. No patient required discontinuation of daptomycin because of adverse effects. Clinical success at treatment completion was achieved in 37 (86%) patients. Three patients died while on treatment with daptomycin. Conclusion In summary, daptomycin was a safe and useful treatment for GPC infection in SOT recipients.
Revista:
REVISTA IBEROAMERICANA DE MICOLOGIA
ISSN 1130-1406
Vol. 31
N° 4
Año 2014
Págs.255 - 261
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.
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN 0066-4804
Vol. 58
N° 9
Año 2014
Págs.5602 - 5605
It is uncertain whether monitoring plasma ganciclovir (GCV) levels is useful in predicting cytomegalovirus (CMV) DNAemia clearance in preemptively treated allogeneic stem cell transplant recipients. In this observational study, including 13 episodes of CMV DNAemia treated with intravenous (i.v.) GCV or oral valganciclovir, we showed that monitoring trough plasma GCV levels does not reliably predict response to therapy. Rather, immunological monitoring (pp65 and immediate-early [IE]-1-specific gamma interferon [IFN-gamma]-producing CD8(+) T cells) appeared to perform better for this purpose.
Revista:
CRITICAL CARE
ISSN 1574-4280
Vol. 18
N° 2
Año 2014
Págs.422
Revista:
ACTAS ESPAÑOLAS DE PSIQUIATRIA
ISSN 1139-9287
Vol. 42
N° 1
Año 2014
Págs.9-17
MS is highly prevalent in Spanish patients with schizophrenia who are overweight. Given that metabolic syndrome is an important risk factor for cardiovascular disease, these patients should receive appropriate clinical monitoring for this syndrome.
Revista:
PLOS ONE
ISSN 1932-6203
Vol. 9
N° 2
Año 2014
Págs.e89747
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.
Revista:
THERAPEUTICS AND CLINICAL RISK MANAGEMENT (PRINT)
ISSN 1176-6336
Vol. 9
Año 2013
Págs.197-205
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
Revista:
PERITONEAL DIALYSIS INTERNATIONAL
ISSN 0896-8608
Vol. 33
N° 4
Año 2013
Págs.458-461
Revista:
NEFROLOGIA
ISSN 0211-6995
Vol. 33
N° 2
Año 2013
Págs.273-75
Autores:
Mensa, J.; Soriano, A.; Llinares, P; et al.
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 26
N° Supl. 1
Año 2013
Págs.1-84
Revista:
CLINICAL DRUG INVESTIGATION
ISSN 1173-2563
Vol. 33
N° 5
Año 2013
Págs.375-381
The absorption of bilastine after oral administration to healthy subjects was rapid. The absolute oral bioavailability was moderate
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 25
N° 1
Año 2012
Págs.17 - 24
Amphotericin B in its lipid formulation continues to be the reference drug in the treatment of systemic fungal infections despite the time elapse since the development of this compound. The absence of fungal resistance, pharmacokinetics, and the better tolerability profile as compared with the remaining formulations of amphotericin B are sufficient reasons to justify its prominent therapeutic role. The liposome containing liposomal amphotericin B is very stable in relation to the presence of cholesterol and phospholipids are not thermolabile, so that free amphotericin B is almost inexistent (<1%), which explains the reduced incidence of effects related to the drug administration, and a reduction in the incidence of nephrotoxicity (half than that with amphotericin B lipid complex) and that even in some studies at doses of 1 mg/kg has been shown to be negligible. This profile explains the very high plasma drug concentrations and the reduced distribution volume and clearance, with a very prolonged elimination half-life. There are evidences showing that the liposome through amphotericin B is capable of binding to ergosterol present in the fungal membrane and only at this moment would be the antifungal released to exert its pharmacological effects.
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 23
N° Supl. 9
Año 2012
Págs.508 - 509
Revista:
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA
ISSN 0365-6691
Vol. 87
N° Suppl. 1
Año 2012
Págs.3 - 9
Revista:
DRUGS OF TODAY
ISSN 1699-3993
Vol. 47
N° 4
Año 2011
Págs.251-262
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.
Autores:
Barberán, J. (Autor de correspondencia); Mensa, J.; Vallejo Llamas, J. C.; et al.
Revista:
REVISTA ESPANOLA DE QUIMIOTERAPIA
ISSN 1988-9518
Vol. 24
N° 4
Año 2011
Págs.263 - 270
Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results.
Autores:
Carreras, Enric; Vázquez, Lourdes; Rodríguez Tudela, José Luis; et al.
Revista:
ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA
ISSN 0213-005X
Vol. 29
N° Supl. 4
Año 2011
Págs.42 - 47
Revista:
CLINICAL INFECTIOUS DISEASES
ISSN 1058-4838
Vol. 50
N° 1
Año 2010
Págs.121 - 122
Revista:
Revista de Osteoporosis y Metabolismo Mineral
ISSN 1889-836X
Vol. 2
N° 2
Año 2010
Págs.35 - 46
Autores:
Candel, F.J.; Martínez-Sagasti, F.; Borges M., M.; et al.
Revista:
Revista Espanola de Quimioterapia
ISSN 0214-3429
Vol. 23
N° 3
Año 2010
Págs.115 - 121
Revista:
REVISTA ESPAÑOLA DE QUIMIOTERAPIA
ISSN 0214-3429
Vol. 23
N° Supl.1
Año 2010
Págs.18-24
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 21
N° Supl. 8
Año 2010
Págs.381
Revista:
MEDICINA CLINICA
ISSN 0025-7753
Vol. 135
N° Supl. 3
Año 2010
Págs.55-59
Daptomycin is a lipopeptide bactericidal antimicrobial indicated in the treatment of skin and soft tissue infections (SSTI), Staphylococcus aureus-related right-sided infective endocarditis (RIE) and bacteremia secondary to these infections. The recommended dosage in patients with previous renal impairment is 4 mg/kg/48 hours in SSTI. There are no data published for SSTI and RIE followed by bacteremia. Based on pharmacokinetic models, the recommended dosage in patients under hemodialysis is 4 mg/kg after dialysis. The present article aims to review of the latest published data on daptomycin use in patients with renal impairment and to relate these findings to preliminary data from the EUCORE registry in Spain.
Revista:
Journal of Pharmaceutical and Biomedical Analysis
ISSN 0731-7085
Vol. 51
N° 4
Año 2010
Págs.875 - 881