Farmacocinética poblacional de cisplatino aplicada a la personalización de su dosificación en pacientes oncológicos

ObjectiveTo develop and internally validate a population pharmacokinetics model for cisplatin and assess its prediction capacity for personalising doses in cancer patients.MethodCisplatin plasma concentrations in forty-six cancer patients were used to determine the pharmacokinetic parameters of a two-compartment pharmacokinetic model implemented in NONMEN VI software. Pharmacokinetic parameter identification capacity was assessed using the parametric bootstrap method and the model was validated using the nonparametric bootstrap method and standardised visual and numerical predictive checks. The final model's prediction capacity was evaluated in terms of accuracy and precision during the first (a priori) and second (a posteriori) chemotherapy cycles.ResultsMean population cisplatin clearance is 1.03 L/h with an interpatient variability of 78.0%. Estimated distribution volume at steady state was 48.3 L, with inter- and intrapatient variabilities of 31,3% and 11,7%, respectively. Internal validation confirmed that the population pharmacokinetics model is appropriate to describe changes over time in cisplatin plasma concentrations, as well as its variability in the study population. The accuracy and precision of a posteriori prediction of cisplatin concentrations improved by 21% and 54% compared to a priori prediction.ConclusionThe population pharmacokinetic model developed adequately described the changes in cisplatin plasma concentrations in cancer patients and can be used to optimise cisplatin dosing regimes accurately and precisely.     

Análisis y minimización del riesgo de rotura de stock aplicado a la gestión en farmacia hospitalaria

ObjectiveTo determine how many dispensary drugs should be in the safety stock in a tertiary hospital in accordance with the risk level and the number of days that the hospital is able to withstand a stockout.MethodsWe statistically analysed the infliximab order recorded over a period of 120 days. This drug is relevant for this study as it is costly and is immediately supplied to the clinic. Using the data records for purchasing and dispensing in our department, we created a table to compare the level of risk assumed with the number of units in stock and the number of days that the safety stock should last. In addition, we calculated how much stock there should be in accordance with different heuristic rules used by pharmacy departments.ResultsIn the period being studied, the daily order was 11.4 ± 14.8 units of infliximab. Using the methodology proposed, we discovered that there should be 79 units in the safety stock. Other hospital rules determine values of 47 and 119 units.ConclusionsThe method proposed allows us to discover the risk level that is assumed when selecting the safety stock. Therefore, we are able to design a safety stock policy consistent with the risk level adopted. Under certain assumptions the safety stock quota provided by this method could be reduced. Lastly, there is a notable difference between the safety stock values suggested by different rules, as it has been shown in this article.     

Effect of Germinated Soy Protein on the Growth of HeLa Cervical Cancer Cells in Female Athymic Mice

Previous studies showed that germination could improve the antiproliferative effect of soy protein on cervical cancer cells and that a peptide fraction (MAPF) from germinated soybeans decreases the expression of PTTG1 and TOP2A (2 genes considered as therapeutic targets) causing apoptosis of cancer cells. The aim of this work was to study the effect of feeding germinated soybean protein diets on the tumor growth in nude mice inoculated with cervical cancer cells and identify the bioactive component. Mice were randomly assigned to 1 of the 6 dietary groups based in AIN-93G formulation with 6 protein sources: casein, ungerminated soy protein (SP), and SP from 2 and 6 days of germination, with and without ethanol-soluble phytochemicals (ESPC). Compared with casein-fed controls, the tumor volumes after 5 wk were reduced by 44.6% by ungerminated SP, 98.9% by 2-day-germinated SP, 97.7% by 2-day-germinated SP without ESPC, 94.7% by 6-day-germinated SP, and 92.7% by 6-day-germinated SP without ESPC (P < 0.05). Liquid chromatography coupled with tandem mass spectrometry analysis of MAPF showed that the bioactive peptide might be the leginsulin, a peptide involved in signal transduction of soybean cells. Germination is a simple procedure that could help to increase the anticancer activity of soy protein probably through generation of biologically active peptides.     

El cáncer colorrectal en España. Costes por incapacidad temporal y opciones preventivas desde las empresas

BackgroundColorectal cancer is one of the most frequent cancers in both sexes and the most frequent in the developed countries, if men and women are considered together as a group. It has an important associated morbidity and mortality in all countries and constitutes a public health problem with a high direct and indirect economic cost. The number of workdays lost due to temporary disability (TD) is one of the quantifiable references of these indirect costs.AimsTo determine the indirect cost associated with TD due to colorectal cancer in Spain during the year 2011, a cost that aids in the prevention cost/benefit estimation.MethodsThe number of TD processes, the number of workdays lost due to TD, and the mean duration of those processes, based on the CIE 9-MC codes related to this pathology, as well as the calculated cost, using the Spanish minimum wage as a reference, during the period of January to December 2011, were all reviewed.ResultsColorectal cancer in Spain during 2011 represented 1,046 TD processes, 202,784 workdays lost, and a mean process duration of 194 days/year. The resulting cost of the pathology due to TD was 4,335,521.92 euros.ConclusionsThese results are beneficial for evaluating the usefulness of implementing public health support strategies for a greater reduction in colorectal cancer prevalence and mortality, and an improvement in quality of life of the affected individuals and their families, together with an economic savings resulting from a reduction in TD as a consequence of this disease.     

Potentiation of arsenic neurotoxicity by folate deprivation: Protective role of S-adenosyl methionine

Folate deficiency contributes to a variety of age-related neurological and psychological disorders including amyotrophic lateral sclerosis (ALS). The environmental neurotoxin arsenic has recently been linked with decreased neurofilament (NF) content in peripheral nerve. We examined herein, whether or not folate deprivation potentiated the impact of arsenic on NF dynamics. Arsenic inhibited translocation of NFs into axonal neurites in culture and increased perikaryal NF phosphoepitopes. Folate deprivation potentiated the impact of arsenic on these phenomena. Supplementation with S-adenosyl methionine (SAM) attenuated the impact of folate deprivation on arsenic neurotoxicity, consistent with the decrease in SAM following folate deprivation and the requirement for SAM-mediated methylation for arsenic bioelimination. These findings demonstrate how key nutritional deficiencies can potentiate the impact of enrivonmental neurotoxins.