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Regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recognize pharmacogenetics as a key tool in their pharmacological guidelines for pharmaceutical counseling. In this context, community pharmacies play a crucial role in addressing this healthcare need, which could lead to a significant improvement in patients' quality of life by preventing ineffective or contraindicated treatments. In this work, we conducted a systematic review of the available scientific evidence regarding druggene interactions relevant to community pharmacy. We identified the main genes and polymorphisms associated with treatment response and adverse effects in primary care. Finally, we propose a model for implementing pharmacogenetic services in community pharmacies. [ABSTRACT FROM AUTHOR]

Ceftiofur is a third-generation cephalosporin widely used in cattle and swine farming to treat respiratory and reproductive conditions. The veterinary pharma industry consistently develops new formulations with this molecule to bring highly effective products to market with short withdrawal periods, ensuring consumer safety for products derived from treated animals. The study aimed to evaluate the plasma concentration profile of Vilocci, a new formulation of ceftiofur, in comparison to the minimum inhibitory concentrations (MIC) of various pathogens commonly found in bovine and swine farming. Ten animals from each species were used, and a single dose of 1 mg/kg was given to bovines and 5 mg/kg to swine. Blood samples were collected at 12 time points to construct the pharmacokinetic profile. The minimum inhibitory concentration (MIC) of growth for the pathogens of interest isolated from the target species was determined and the effectiveness of the for; mulation was assessed for each one. [ABSTRACT FROM AUTHOR]

Currently, the field of phytopharmacology has demonstrated the antidiabetic potential of several traditional plants, including Pseudoelephantopus spicatus (amargon); however, studies demonstrating the hypoglycemic effect of this plant are little known. Therefore, in the present study, its glycemia-regulating effect was evaluated in a Wistar rat model. The experiments were performed as a pilot test and were validated in a kinetic of 0, 1, 1, 2, 6 and 24 hours using five experimental groups (control, diabetics induced with alloxan, diabetics treated with metformin and diabetics treated with P. spicatus extract with doses of 250 and 500 mg/kg). The treatments were applied for 1, 5 and 21 days and the data obtained were validated by ANOVA/Neuman-Keuls (p< 0.05) using the GraphPad Prism V.5. statistical package. The results showed that alloxan at 120 mg/kg induced diabetes mellitus in 100 % of the rats. The extract at 250 and 500 mg/kg achieved a significant reduction in blood glucose levels compared to diabetic rats, showing no significant difference between doses. The reduction in blood glucose levels caused by metformin at 500 mg/kg p< 0,05, and the different doses of the extract showed no significant differences. According to the results of the study, the extract of P. spicatus induces a hypoglycemic effect in rats. [ABSTRACT FROM AUTHOR]

The relationship between cardiac output and anesthetic drugs is important to anesthesiologists, since cardiac output determines the speed with which a drug infused into the bloodstream reaches its target and the intensity of the drug's effect. But rather than focus on how anesthetic drugs affect cardiac output, this narrative review focuses on how changes in cardiac output affect the pharmacokinetics and pharmacodynamics of general anesthetics during the three phases of anesthesia. At induction, an increase in cardiac output shortens both the onset time of propofol for hypnosis and the neuromuscular blocking effect of rapid-acting neuromuscular blockers, favoring the conditions for rapid sequence intubation. During maintenance, changes in cardiac output are followed by opposite changes in the drug plasma concentration of anesthetic drugs. Thus, an increase in cardiac output followed by a decrease in the plasma concentration of the anesthetic could expose the patient to a real risk of intraoperative awakening, which can be avoided by increasing the dose of hypnotic drugs. At emergence, an increase in cardiac output secondary to an increase in pCO2 allows for a more rapid recovery from anesthesia. The pCO2 can be increased by adding CO2 to the respiratory circuit, lowering the ventilatory rate, or placing the patient on partial rebreathing. Finally, the reversal action of sugammadex for rocuronium-induced neuromuscular block can be shortened by increasing the cardiac output. [ABSTRACT FROM AUTHOR]

Through this work, the pharmacokinetics of Norfloxacin in pigeons were explored by using six healthy male pigeons as the subjects for this study. The pharmacokinetic indices of orally administered Norfloxacin were obtained by microbiological assay and then the data were fitted to the two-compartment pharmacokinetic open model to evaluate the distribution and excretion parameters. In the achieved results, the calculated absorption rate constant (Kab) was 1.26 h-1, the maximum achieved concentration of Norfloxacin was 2.75 μg/ml at 1.34 hr., the volume of distribution (Vd/F) was 3.15 L/kg. The half-life (t1/2β) was 4.9 hrs., the calculated area under the curve of Norfloxacin (AUC0-t) was 16.75 (h*μg)/ml, while the clearance of Norfloxacin (Cl/F) was 0.49 L/hr/kg. In conclusion, the pharmacokinetic parameters of Norfloxacin in pigeons are not far away from other birds like chickens, considering the differences among them. Norfloxacin is a valuable antibacterial agent against susceptible bacterial infections depending on the obtained pharmacokinetic profile. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), which for the most part comprises Crohn’s disease (CD) and ulcerative colitis (UC), is an immune-mediated inflammatory disease that presents with alternating periods of inflammatory activity and remission, mainly affecting the intestine. Treatments using monoclonal antibodies have revolutionised the management of IBD patients, with the aim of controlling and suppressing inflammatory activity, and promoting healing of the mucosa and other compromised tissues. Agents currently indicated for this use include: infliximab, adalimumab and golimumab (for UC only), vedolizumab, ustekinumab, tofacitinib (for UC only), and filgotinib (for UC only). Despite the positive impact that these agents have had in the management of patients with IBD, there is significant intraindividual and interindividual variability with respect to response to these drugs, and it is not possible to achieve a total cure. Approximately one-third of IBD patients do not respond to tumour-necrosis-factor-alpha antagonists (anti-TNFα), and of those who show a response initially, a subsequent loss of response to treatment may occur in up to 40% of patients within the fi rst year of treatment. Ustekinumab is an IgG1 human monoclonal antibody that binds to the p40 subunit of interleukins 12 and 23 which has been shown to be effective in both inducing and maintaining clinical remission. Its efficacy following treatment intensification at 4-6 weeks is 50%, and reinduction has also been described as a possible strategy in cases where treatment has been discontinued due to surgery, or where there has been a loss of response. A number of recent prospective and retrospective studies have demonstrated a positive exposure-response relationship between ustekinumab concentration and clinical remission, making it possible to optimise the treatment response. Pre-dose concentrations of ustekinumab (Cmin UST) in the studies reviewed were higher in responders as compared to nonresponders, in both the induction and maintenance phases. [ABSTRACT FROM AUTHOR]

Pain is a complex and highly prevalent symptom in advanced oncological disease. Often, balancing analgesic control and toxicity poses a great challenge for healthcare professionals. This clinical case demonstrates the importance of a good anamnesis of oncological pain and an individualized treatment, considering the characteristics of the pain and the available drugs in order to achieve analgesic efficacy while minimizing adverse effects and, thus, improving the patient's quality of life. [ABSTRACT FROM AUTHOR]

Introduction. The World Health Organization (WHO) estimates that more than 40% of pregnant women worldwide have anemia, and that half of them suffer from iron deficiency. The prevalence of this in Latin America is 40%, and in Colombia, 44.7%. Physiologically, a problem called "dilutional anemia" occurs during pregnancy. There are conditions in pregnant women that predispose them to suffering from pathological anemia. The latter is mainly caused by iron deficiency, hence the importance of diagnosing this entity on time and starting treatment. Iron administration is the basis of treatment of anemia caused by iron deficiency. It can be administered orally, which is the preferred option in the majority of patients. However, when this is not possible, parenteral iron must be used. However, parenteral iron is rarely used as the first line of treatment of gestational anemia. The objective of this article is to carry out a review that allows for the identification of therapy with parenteral iron as an efficient alternative for the treatment for gestational anemia, considering the pharmacological characteristics, administration, and use among the different molecules available in Colombia. Methodology. We carried out a search in databases and electronic libraries. The criteria considered were texts published between 1996 and 2020 in Spanish and English. 95 articles were obtained, of which 49 were selected. The keywords for their search were physiology, parenteral iron, gestational anemia, iron deficit, pregnancy complications, iron compounds, pharmacokinetics, diagnosis, and treatment. Division of Covered Topics. Physiology; diagnostic aids; pharmacological characteristics of parenteral iron; advantages, indications, and contraindications of parenteral iron; secondary effects and application method. Conclusions. Parenteral iron is a safe and efficient treatment to handle anemia during pregnancy. The indications and pharmacology of the molecules must be considered to choose the most appropriate option. In addition, it replaces iron reserves and hemoglobin levels more quickly. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are among the most widely used drugs in the world, due to their low cost, extensive prescription and effectiveness. However, its long-term use is not safe and there are still certain gaps in the knowledge of the proper use of these drugs. Therefore, this review aims to expose their general properties as well as their true indications, the appropriate long-term use and strategies to achieve adequate deprescription of these drugs, seeking to avoid indiscriminate use. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is the most prevalent autoimmune, inflammatory, chronic and degenerative disease worldwide, with relapsing-remitting MS being the most common form of the disease. Natalizumab, an IgG4 monoclonal antibody that binds to the integrin a4ß1 on the surface of leukocytes and thereby prevents them from migrating into the central nervous system, was approved for the management of severe RRMS. At the approved fixed intravenous dose of 300 mg administered every 4 weeks, it has been demonstrated that more than 90% of patients achieve pre-infusion serum concentrations of NTZ >10 µg/mL, whilst efficacy has been demonstrated at levels of 2.5-10 µg/mL. A plasma NTZ concentration of 2.5 µg/mL achieves 50% biophase occupancy and has demonstrated therapeutic efficacy, whilst occupancy rates of between 20 and 40% have been associated with an increase in disease activity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the vancomycin effectiveness against grampositive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial. [ABSTRACT FROM AUTHOR]

Copaifera reticulata Ducke is a medicinal plants greatly employed in northern and northeastern Brazil. However, skin penetration is difficult when it is applied in natura. However, permeability increases through nanoformulations and phonophoresis and low frequency ultrasound that increases skin permeability of compounds. The effect of oil-resin of copaiba, in natura and in gel (nano-emulsion), associated to phonophoresis, was analyzed and compared for muscle repair in Wistar rats. Copaiba nano-emulsion was formulated by phase inversion. It was incorporated to hydrogel Carbopol® (20% nano-emulsion, 80% Carbopol®). Male animals (n=24) were divided into six groups and later underwent traumatic lesion of the gastrocnemius muscle. Muscle repair was analyzed by plasmatic dosage of aspartate aminotransferase (AST) and kinase creatine (CK). Results show that topic treatments with oil-resin, associated with phonophoresis and nanogel were efficient in the assay for the repair of skeleton muscles. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare tissue and plasma concentrations of florfenicol (FFC) and its metabolite florfenicol amine (FFC-a) between sheep and rabbits, after intramuscular administration of 20 mg FFC/kg. Materials and methods. Five Suffolk Down sheep and six New Zealand rabbits were used in this study. Blood samples were collected before FFC administration and at 0.25, 0.5, 1, 1.5, 2, 3 and 4 hours after treatment. At 4 hours after treatment, euthanasia was applied to animals. Plasma and tissue concentrations of FFC and FFC-a were determined by HPLC. Results. For FFC, maximum plasma concentrations, absorption rate, absorption half-life, distribution rate, and area under the plasma concentration-time curve were all found to be significantly higher in rabbits than in sheep. Similarly, for FFC-a, significantly higher maximum plasma concentrations and area under the concentration-time curve were observed in rabbits as compared to sheep. The metabolite ratio was higher in rabbits (12.7±3.07%) compared to sheep (3.99±0.87%) (p<0.05), as were the tissue concentrations of FFC and FFC-a. Conclusions. Significant differences in the pharmacokinetics and tissue concentrations of FFC, and its metabolite FFC-a, were observed between these two animal species. The higher concentrations of FFC-a in rabbits indicate a greater level of FFC metabolism as compared to sheep. This should be considered when establishing dosage and frequency of FFC administration for rabbits. [ABSTRACT FROM AUTHOR]

Evaluar la utilidad de la determinación de concentraciones séricas (Cs) de adalimumab (ADA) como factor predictor de la adherencia al fármaco medida a través de la tasa de posesión de medicación (TPM) y del test de Morisky Green (MG) en pacientes con enfermedades crónicas inflamatorias. Diseño prospectivo, descriptivo de cohortes. Criterios de inclusión: pacientes adultos con artropatías inflamatorias (AI) o enfermedad inflamatoria intestinal (EII) en tratamiento con ADA. Criterios de exclusión: pacientes con anticuerpos anti-ADA. Variables: sexo, edad, diagnóstico, pauta posológica, Cs (μg/ml), TPM (TPM ≥ 80% adherentes), y resultado del test de MG (no adherente o adherente). El análisis estadístico se realizó mediante STATA v13.0. Cuarenta y cinco pacientes (23 mujeres) con edad de 52,22 (14,39) años, 17 EII (37,78%), 26 AI (57,78%) y 2 con ambas enfermedades (4,44%) tratados con ADA cada 14 días (42/45,93,33%) o cada 7 días (3/45;6,67%). Se detectaron Cs infraterapéuticas en el 22,22% pacientes (10/45): el 10% (1/10) se clasifican como no adherentes y el 90% (9/10) como adherentes según MG y TPM. La Cs con la TPM, así como los métodos indirectos entre sí (TPM y MG) presentaron un índice de acuerdo débil, siendo la asociación ligeramente superior al relacionar los métodos indirectos entre sí (0,244 vs. 0,378). La determinación de Cs de ADA presenta, por sí sola, una utilidad limitada en la detección de pacientes no adherentes. to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases. Design a prospective descriptive cohort study. Inclusion criteria: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA. Exclusion criteria: positive anti-adalimumab antibody. Variables: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0. Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40 mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378). the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients. [ABSTRACT FROM AUTHOR]

Ibuprofen, 2-(3-isobutylphenyl) propanoic acid, is a racemic mixture of a weak acid compound, broadly used since the seventies of the last century as a non-steroid anti-inflammatory drug to treat mild to moderate pain, fever and inflammation. It presents a low incidence of severe gastrointestinal side effects, which imply no risk for the patient. Oral administration is the most frequently used route of administration and in this regard, there exist many different formulations. For instance, salt formation is a common technique to optimize drugs solubility and dilution along the gastrointestinal tract, which is achieved by association with ions or amino acids. Ibuprofen arginine salts accelerate absorption, decrease the latent period and the time taken to reach the maximum concentration, and increase the analgesic potency and the maximum serum concentration of the drug, while improving its toxicological profile, without significantly affecting its bioavailability, distribution or elimination rate. [ABSTRACT FROM AUTHOR]

Leflunomide is an antirheumatic drug with anti-inflammatory and antirheumatic properties, it is rapidly metabolized in the body to the active metabolite teriflunomide, which causes its pharmacological activity. At the usual 20-mg daily dosage of leflunomide, the expected teriflunomide plasma concentration is about 35 µg/ml. The pharmacokinetics of the drug is characterized by a large interindividual variability and a long half-life, which in combination with possible side effects creates the need to control the concentration of teriflunomide in the blood plasma. Teriflunomide may increase the risk of fetal death or teratogenic effects when administered to pregnant women. Teriflunomide plasma concentrations less than 0.02 µg/ml are preferred for patients anticipating pregnancy. In this study, a sensitive and high-performance method for analyzing teriflunomide in human blood plasma in a wide range of concentrations was developed and validated using a triple quadrupole liquid chromatography-mass spectrometer (HPLC-MS/MS). Sample preparation was performed by protein precipitation with acetonitrile, followed by chromatographic separation using an Acquity UPLC BEN C8 1.7 mm, 2.1 x 50 mm column (Waters, USA). D4-teriflunomide was used as an internal standard. The developed method was validated in the concentration range from 0.001 µg/ml to 200 µg/ml teriflunomide in plasma. Accuracy (%), defined as the difference between the nominal and measured concentration and reproducibility (coefficient of variation CV) ranged from -5.02% to 5.00% and from 0.47% to 9.30%, respectively, within the series and between series of samples. The developed method was successfully used to analyze volunteer blood plasma samples after taking 20 mg of leflunomide. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAb) represent one of the therapeutic groups of greatest interest in drug development. Because of their complexity (both structural and functional), pharmacokinetic monitoring of biological drugs are essential in routine clinical practice. Absorption of mAb after intramuscular or subcutaneous administration may occur via blood or lymph, and its distribution depends on the mechanism of extravasation, the affinity of mAb for tissue components and tissue clearance (CL). Elimination occurs mainly by intracellular proteolysis following specific (receptormediated) or non-specific endocytosis. On the other hand, the catch and subsequent release of mAb, the redistribution of blood flow by physiological processes, the formation of complexes and the process of recycling through the Brambell receptor are the physiological mechanisms that condition intra-individual pharmacokinetic variability. Furthermore, immunogenicity to mAb, patient weight, and the amount of target antigen are the main factors affecting pharmacokinetic variability. [ABSTRACT FROM AUTHOR]

Introduction: The new generations of Cuban doctors face the medicalization of society, where precision medicine, articulated with the reasoned therapy is aim to increase the quality of the prescription process. However, the current scenario reveals the need to promote the rational use of medicines according to the development of the country through education, from instruction. Antecedents: In previous courses the topics that have been addressed have been those of greatest difficulty reflected in the evaluation system of the subject Pharmacology-I. The absence of a teaching support material coherent with the indications of the Director Program of the Teaching of Medical Sciences, the objectives of the discipline and in response to the current need of the teaching-educational process were elements that supported its design. Objective: Contribute to the rational prescription of medications through the contents of pharmaceutical forms, routes of administration and pharmacokinetics using the brochure during self-preparation. Methods: A pedagogical tool with a didactic approach was designed, aimed at undergraduate students of the medical career. It is structured in introduction to the content, 29 questions (objective test, modified essays), answers and reference bibliography. Self-assessment is achieved by the checklist. The way of conceiving basic contents to teach prescription habits, their systematic use during selfpreparation, linked with the professor consultation, promote the gradual development of cognitive independence, major level of knowledge assimilations and resolutive and scientific capacity. Conclusions: The divulgation on the university website, its implementation and systematic use by students, indicates to be a relevant tool to promote good prescription skills and habits. The approach aimed at self-preparation encourages self-management of knowledge and contributes to the formation of the professional model in correspondence with the task that society demands. [ABSTRACT FROM AUTHOR]

Objetivo: Desarrollar y evaluar dos formulaciones parenterales que incrementen la biodisponibilidad de albendazol. Antecedentes: El albendazol (ABZ) es el fármaco de elección para tratamiento de neurocisticercosis. Se ha demostrado que inhibe la polimerización de la tubulina, lo que provoca la degeneración de los microtúbulos y la muerte del parásito. Un factor limitante para su uso es su baja solubilidad, lo que genera una gran variabilidad interindividual en las concentraciones plasmáticas. Aunque la vía oral es la más común por su comodidad, la vía parenteral se presenta como una alternativa viable para alcanzar las concentraciones plasmáticas deseadas. Métodos: El estudio se llevó a cabo con el apoyo del proyecto UNAM-DGAPA-PAPIIT IN206122. Se desarrollaron dos formulaciones parenterales utilizando dos enfoques: la síntesis de un profármaco fosfonooximetilado y una nueva formulación empleando cosolventes. Después de sintetizar el profármaco de ABZ, se evaluó su solubilidad e hidrólisis con fosfatasa alcalina. Para la formulación con cosolventes se seleccionó una mezcla de etanol-dimetilacetamida-polietilenglicol 400, y se determinó su estabilidad y actividad hemolítica. El estudio de farmacocinética se llevó a cabo en conejos Nueva Zelanda, a los cuales se les administraron ambas formulaciones por vía intravenosa a dosis de 15 mg de ABZ. El profármaco se administró por vía intramuscular a la misma dosis. Como producto de referencia se utilizó una suspensión de ABZ por vía oral a dosis de 32 mg. No. de registro en el INNN: 95/20. No. de aprobación del protocolo: FQ/CICUAL/435/21. Resultados: La solubilidad del ABZ aumentó en 20000 y 6000 veces con las formulaciones de profármaco y cosolventes, respectivamente. El profármaco se hidrolizó rápidamente, con una vida media de 8.72 ± 0.23 min. La formulación con cosolventes no ocasionó hemólisis y fue estable por al menos 12 meses a temperatura ambiente. En el estudio farmacocinético, se encontró que ambas formulaciones parenterales mostraron mayores concentraciones plasmáticas de ABZ durante las primeras 2 h en comparación con la vía oral. La biodisponibilidad absoluta del ABZ oral fue del 15.5%, mientras que para el profármaco por vía intramuscular fue del 102.6%. Conclusiones: La administración parenteral de ABZ permitió una mayor exposición al albendazol. La formulación con cosolventes podría ser una buena opción para el tratamiento tomando en cuenta su facilidad de preparación y su buen comportamiento farmacocinético. [ABSTRACT FROM AUTHOR]

Objective: Analyze the microbiological effectiveness, based on the pharmacokinetics/ pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. Methods: This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Results: Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10μg/mL and 15μg/mL. Conclusion: The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/ pharmacodynamic target for minimum inhibitory concentration of 1μg/mL. [ABSTRACT FROM AUTHOR]

Pharmacokinetics together with the pharmacodynamics of drugs are the basis for establishing any therapeutic protocol, so knowing, understanding and applying the pharmacokinetic principles of cytotoxic substances contribute to optimizing the treatment. The steps by which an antineoplastic agent passes through the body after administration, namely absorption, transport, metabolism and elimination, influence the clinical outcome. The role of the pharmacokinetics of cytostatic chemotherapies is to achieve maximum efficacy of the active substances while preventing and reducing their toxicity. Making a complete and correct pharmacological profile of cytostatics is an essential step in oncology, and this can only be done by deepening the pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Varenicline is a medication used for smoking treatment that acts as a partial agonist for nicotinic cholinergic receptors a4p2 and a3p4 and as a total agonist of receptor a7 in the central nervous system. Pharmacokinetic is important information for medications that acts in the central nervous system. This kind of assay is commonly done by expensive and complex analytical techniques. Therefore, the aim of this study was to evaluate the possibility of using the open field test as a pharmacokinetic model for varenicline in male rats exposed to a single dose of varenicline. Male rats received a single dose orally (gavage) of three different concentrations of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg or water (control group). The open field observations were recorded 30 min, 1, 2, 4, 6, 24, 48, 72 h and 7 days after the administration of varenicline or water. The results showed alterations in locomotion and rearing frequencies, as well as in immobility time observed in open field, which is consistent with this drug's plasma peak. Consequently, this behavioral test apparently can be considerate as a model for pharmacokinetic evaluation of varenicline. [ABSTRACT FROM AUTHOR]

The relationship between the dose and plasma concentration of a drug is determined by pharmacokinetics. However, difficulties arise when more than one drug is administered simultaneously. There is currently a gap in the teaching model when trying to convey the significance of pharmacodynamic interactions. In this article the authors reflect on the importance of developing a software that simplifies the pharmacokinetic concepts of two drugs, turning them into one single variable in space as a function of time. Together with depth of anesthesia monitoring and the pain control variables, this model will bring pharmacokinetics and pharmacodynamics together and provide a teaching tool for improved understanding of these concepts. [ABSTRACT FROM AUTHOR]

This paper aimed to study the disposition of danofloxacin in broiler chickens in order to establish pharmacokinetic parameters in plasma and tissues and to estimate a withdrawal period. 42 adult chickens were divided into 14 groups of 3 individuals each, who received a single oral dose of 5 mg/kg of danofloxacin after a fasting period of 12 h before and 3 h post-administration. Each batch was sacrificed at pre-established times, and blood, muscle, and liver samples were obtained over a period of up to 120 h post-application. The assay consisted of the liquid-liquid extraction of analyte and its separation and quantification by high-performance liquid chromatography (HPLC). Time averages for plasma and tissue concentration were analyzed using the PK Solution software. Withdrawal period was calculated using the WT 1.4 program, based on maximum residue limits (MRL) of 200 and 400 μg/kg, established for chicken muscle and liver, respectively. Danofloxacin exhibits a rapid absorption, resulting in a Cmax of 1.1 μg/ml with a Tmax of 1 h; t1/2β (h) was 7.64; 6.16 and 12.77 in plasma, liver, and muscle, respectively; a Vd of 5.51 L/kg; tissue/plasma ratios of 0.48 and 6.61 in muscle and liver, respectively, and levels up to 72 h. Based on residual concentration analysis, a withdrawal period of 1.4 and 3.34 d was estimated for muscle and liver, respectively [ABSTRACT FROM AUTHOR]

Drug interactions represent the cornerstone in the basic anesthetic triangle and knowledge about such interactions contributes to a solid foundation for administering medications. This article dwells on the anesthetic drug interactions: pharmaceutical (mixing or not mixing), pharmacokinetic (alterations in distribution, metabolism, or clearance), pharmacodynamics (synergism, additive effect) and thermodynamic (affinity and intrinsic activity). The basic anesthetic triangle is a current concept and drug interactions are the cornerstone for safe anesthesia. These interactions are currently neglected and hence the anesthetist should recognize any drug interactions for a safer practice of anesthesia. [ABSTRACT FROM AUTHOR]

Nonbiological immunosuppressive therapy is frequently used in dermatological daily practice in a large number of inflammatory dermatoses. Its use should be based on the understanding of its pharmacology: mechanism of action, pharmacokinetics and adverse effects, allowing the dermatologist to realize adequate monitoring and opportune screening and prophylaxis prior to its use. [ABSTRACT FROM AUTHOR]

From its isolation and its beginning to the present day, vancomycin occupies a prominent role as an important antimicrobial reserved for the treatment of serious infections caused by microorganisms of relevance in the nosocomial environment. Thus, the objective of this study was to gather information about this antimicrobial. It is a version of the literature that uses electronic databases to cross the descriptors' vancomycin, glycopeptide, Streptomyces as well as their respective correspondents in the English language. Vancomycin belongs to the class of glycopeptides and is considered to be bactericidal by preventing cell wall synthesis having as its target structure a D-alanine, D-alanine portion of the bacterial cell wall. Vancomycin is an antimicrobial available especially for parenteral use and should be administered intravenously and due to observed adverse reactions monitoring of its use is necessary and is reserved for the treatment of serious infections. However, vancomycin-resistant microorganisms are a challenge for a medical clinic, where inadequate therapeutic practices on the part of health professionals lead to the emergence of resistant microorganisms. In addition, antimicrobial resistant bacteria are common not only in the nosocomial environment, but also in communities. [ABSTRACT FROM AUTHOR]

Ehrlichia canis is the causative bacterium of canine monocytic ehrlichiosis (CME), a disease of global importance in veterinary and human medicine. Several studies have addressed the therapeutic efficacy of tetracycline hydrochloride and doxycycline hyclate (HD) for the treatment of CME, however the results are still controversial. Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well characterized disease that can serve as a model for research in diseases of the Rickettsial order and tick-borne zoonoses. Although the pharmacokinetics and efficacy of the treatment in the acute and subclinical CME phases have been known for decades, some results also indicate that Ehrlichia canis may persist in clinically normal dogs, even after an extensive treatment regimen. The purpose of this review is to (major delve into/further investigate) the pharmacokinetics and side effects of doxycycline in the treatment of canine ehrlichiosis. [ABSTRACT FROM AUTHOR]

Introduction: The use of total intravenous anaesthesia (TIVA) has been growing worldwide over the past 20 years due to the creation of new drugs and the development of new targetcontrolled infusion pumps, many of which have already been approved in the United States by the FDA (Food and Drugs Administration), in Europe and in Colombia. However, the use of TIVA has not been expanded yet as part of routine practice. Objective: To determine the frequency of TIVA use in our country and to identify existing barriers for its implementation. Materials and Methods: Survey designed to determine the use of TIVA in general anaesthesia practice in Colombia. A representative random sample of the universe of anaesthetists registered in the database of the Colombian Society of Anaesthesiology and Resuscitation (S.C.A.R.E.) was calculated. Reminders were sent by e-mail and some of the selected respondents were contacted by phone. Results: Overall, 141 (32.4%) responses were obtained. The frequency of TIVA use was reported as Always, 7 (5.0%), Almost Always, 52 (36.9%), Hardly Ever, 57 (40.4%) and Never, 25 (17.7%). The technology used for TIVA administration included macro drip devices (n = 30; 21.3%), volumetric pumps (n = 76; 53.9%), TCI pumps (n = 45; 31,9%), and computer programs (n = 9; 6.4%). The limitations identified for the use of TIVA included low availability of anaesthesia depth monitoring (n = 68; 48.2%) and infusion pumps (n = 52; 36.9%), lack of experience (n = 41; 29.1%), little availability of workshops (n = 26; 18.4%), low availability of medications (n = 23; 16.3%), fear of intra-operative recall (n = 22; 15.6%), limited knowledge of pharmacology (n = 18; 12.8%), increased anaesthesia time (n = 13; 9.2%), and perceived difficulty for performing the technique (n = 13; 9.2%). Conclusions: The use of TIVA has been limited by the low availability of technology, lack of experience or knowledge among anaesthetists, and a preference for the balanced anaesthesia technique. Many anaesthesiologists prefer balanced techniques for general anaesthesia. Some devices used for TIVA administration raise concerns about patient safety. [ABSTRACT FROM AUTHOR]

Plasma and urinary disposition of marbofloxacin was studied in canines (n = 6) after intramuscular administration of 2 mg/kg. At different times post-administration, blood samples were collected until 24 h, and urine samples, only from male dogs (n = 4) at 4; 8; 12, and 24 h. Liquid-liquid extraction of analyte with water, methanol, and centrifugation at 13500 rpm at 4 °C were performed. Separation and quantification were made using HPLC by reverse phase isocratic elution with a C18 column, fluorescence detector at 295 nm excitation and 490 nm emission, and a mobile phase consisting of water, acetonitrile, and triethylamine. Temporary plasma concentrations were analyzed with non-compartmental PK Solution 2.0 software. The results obtained indicate rapid absorption, as well as rapid and wide distribution. Cl and values of t1/2β and MRT indicate slow clearance and prolonged stay. The study evidenced plasma concentrations up to 24 h, which exceed the MIC of relevant pathogens. The AUC/MIC ratio indicates efficacy against microorganisms with MIC ⩽ 0.15 μg/ml. Urinary levels of marbofloxacin are more significant than plasmatic levels. However, new studies are required to assess their use with the tested dose and route of application. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacology of infants is understudied and different from other populations. Objective: To review the unique features of neonatal and infant physiology that impact drug handling and the pharmacokinetics of analgesics, including opioids, ketorolac and acetaminophen. Materials and Methods: This article is a narrative review of the literature from the authors' point of view that constitutes a summary of the information presented at the annual Colombian Society for Anesthesia meeting in Cali, Colombia June 2015. Conclusions: Pharmacology in neonates and infants is unique and must be considered in this vulnerable population. Recommendations for administration of these analgesics are presented based on their unique pharmacokinetic properties. Individual patient variation and clinical response must also be taken into account. [ABSTRACT FROM AUTHOR]

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful. [ABSTRACT FROM AUTHOR]

Introduction. In 1998, an unexplained drug-drug interaction between valproic acid (VPA) and ibuprofen was reported. VPA has been considered a moderate inhibitor of several metabolic enzymes, but recently its inductive properties have been described, including the possibility of auto-induction. Ibuprofen can displace VPA from the plasmatic protein, increasing its serum free concentration, and subsequently its pharmacological actions, including auto-induction. The objective of this article is to describe a similar case and to contribute to the clarification of the underlying pharmacokinetic mechanisms. Methods. A 29-year-old Spanish Caucasian male with schizophrenia was followed with steady-state trough serum concentrations of VPA and clozapine for 5 years, including 3 ibuprofen trials. The main outcome variable was the concentration-to-dose (C/D) ratio, a measure of the ability to eliminate a drug. Independent sample Mann-Whitney U tests were performed to compare C/D ratios. Results. Five VPA C/D ratios, contaminated by VPA auto-induction occurring during or shortly after the two latter ibuprofen trials, were significantly lower (p<0.001) than the other 34 VPA C/D ratios of VPA not contaminated by auto-induction. During the highest ibuprofen dose in the third trial, the patient had two very low clozapine C/D ratios, which were significantly lower than the other 26 clozapine C/D ratios (p=0.021). Conclusions. Reduction in total VPA concentrations could be explained by ibuprofen displacing VPA from the plasma proteins, increasing the serum free VPA. This may induce the metabolism of VPA (and clozapine) and subsequently decrease their serum total concentrations. [ABSTRACT FROM AUTHOR]

Introduction: There are two different pharmacokinetic models (Marsh and Schnider) for the administration of total intravenous anesthesia with propofol, the parameter differences could have some impact over the depth of anesthesia. Objective: To determine if there is a significant difference in the variability of depth of anesthesia suggesting that one model is superior in achieving a more stable and predictable depth of anesthesia during surgery. Methods: A cross-over clinical trial was conducted on 16 healthy patients programmed for upper or lower limb ambulatory orthopedic surgery. Patients were randomly assigned to (i) effect site target controlled infusion of propofol with Marsh model at a target concentration of 2.5 μg/ml for 20 min, a 20 min washout, then propofol was administered with Schnider model at the same effect site target for the reminder of the surgery, or (ii) the reverse sequence. Differences in variability of depth of anesthesia, were assessed by comparing records of spectral entropy indices during surgery through an unpaired t-test. Results: There was no evidence of significant difference in the mean variances of either spectral entropy indices between the two models (p-value: 0.57 for State Entropy, p-value: 0.51 for Response Entropy). Conclusion: The study suggests that both pharmacokinetic models are equivalent in terms of stability of depth of anesthesia. It is important to keep testing determinants of the efficacy of the models in different types of population because their behavior according to individual characteristics of patients or variables such as cost-effectiveness could end up tilting the scale. [ABSTRACT FROM AUTHOR]

BACKGROUND: Homemade fractions of metformin tablets to adjust paediatric doses are difficult to administer, unstable and yields variable doses. In this work, a liquid extemporaneous formulation of metformin, sweetened with 1% sucralose, is proposed. PURPOSE: To determine the pharmacokinetics of the new formulation compared to the fractionated tablet in healthy adult volunteers and to demonstrate that it remains unaltered. METHODS: Randomised, crossed and longitudinal clinical trial, in 12 healthy adult volunteers, 7 males and 5 females (n=12), 24.3 ± 1.8 years, with BMI = 24.9 ± 2.5. Eight blood samples were obtained in Whatman 903® cards at 0, 0.25, 0.5, 1, 2, 4, 8 and 12 hours after administration of 250 mg metformin. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol. Detection was car- ried out by UPLC and tandem mass spectrometry. Mobile phase: 5 mM ammonium acetate and ACN (80:20; v/v), 0.25 mL/min, isocratically. Pharmacokinetics was determined using WinNonlin Pro 3.1 software and analysed by one-way ANOVA (p ≤ 0.05). RESULTS: The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r=0.9982). Samples were stable at 4°C for 17 hours and for 2 months at -80°C. The metformin formulation had a Cmax of 652 ng/mL and 550 ng/mL in the tablet. Tmax and ke were lower with the formulation (1.6 h vs. 1.8 h and 0.32 h-1 vs. 0.29 h-1). The AUC0-12 was virtually the same in both forms (F%=1.01). CONCLUSIONS: The liquid formulation of metformin showed similar pharmacokinetics to the split tablet, but it additionally allows a more precise dose adjustment, ease of administration and uniformity of content. [ABSTRACT FROM AUTHOR]

Recent progress in medical knowledge has indicated that both clinical and biological markers will determine the response to different medical treatments: age, gender and genetics will determine the success of treatment. Genetic variability in this respect is fundamental and determines efficiency and safety of drugs, as well as susceptibility and illness' development. Fortunately, personalized medicine now offers individually tailored treatment strategies for each patient's needs. This is of outmost importance in oncology, since treatment is per se toxic and the commonly found low serum drug concentrations result in low treatment efficacy. Personalized medicine will allow a better approach to this, until now, a poorly managed disease. In this review we intent to raise awareness of personalized medicine and of clinical pharmacologic monitoring, with the aim to achieve adequate levels of efficacy and safety in the use of the cytotoxic drug 5-Fluorouracil (5-FU). Additionally, the importance of pharmacogenomics for the use of 5-FU is discussed. We designed this discussion towards medical practitioners challenged with treatment decisions every day, together with their patients. [ABSTRACT FROM AUTHOR]

Introduction: Remifentanil and propofol infusion using TCI pumps has proven to be beneficial for the practice of anesthesia but the availability of these systems is limited. Objective: Designing a pharmacokinetic model-based algorithm for calculating manual infusion regimens to achieve plasma and effect-site concentrations that may be used in volume infusion pumps, and to compare the difference between the desired and the forecasted concentrations via pharmacokinetic simulation. Methods: Using the Minto & Schnider models for remifentanil and propofol respectively, the algorithm was implemented on an iTIVA application (interactive TIVA) for iOS and Android operating systems. The performance of the algorithm was evaluated estimating the infusion regimens for achieving different effect-site concentrations for induction and maintenance in 34 theoretical patients for 240 minutes. Results: The infusion regimens obtained for remifentanil and propofol resulted in less than 5% average systemic deviation versus the target effect-site concentrations during induction and maintenance. Only one induction infusion was required for remifentanil and propofol. Just one infusion rate was required for remifentanil during maintenance, and between 2 to 5 infusion rate changes for propofol to maintain a stable concentration. The iTIVA-based algorithm estimates concentrations similar to the TivaTrainer® software. Conclusions: The performance of the algorithm to achieve effect-site concentrations during induction and maintenance for remifentanil and propofol was excellent, with a low systemic deviation versus the desired target concentrations. [ABSTRACT FROM AUTHOR]

Objective. Determine the status of analytical laboratories that quantify immunosuppressants in transplant patients who are under therapeutic drug monitoring (TDM) for these drugs in Argentina in order to identify potential perfectible areas for action. Methods. A survey of the clinical and analytical TDM centers in Argentina was conducted between September 2013 and November 2014 under the direction of the Garrahan Hospital Clinical Pharmacokinetics Unit and the National Unified Central Institute for Ablation and Implant Coordination. Results. A nationally representative sample of 27 clinical and analytical centers was identified, of which 45% were public hospitals. Most of these centers (95%) monitor ciclosporin and tacrolimus, and to a lesser extent, sirolimus and everolimus; a small number of them also monitor mycophenolic acid. The median number of samples of these five drugs analyzed per month was 251 (range: 10-2024). Nearly 60% of the samples were analyzed in private institutions. Only four of the respondents (17%) reported values within the therapeutic margin. Of all the centers, 92% use immunoassay as the analytical methodology. Of the bioanalytical installations that have their own facilities, 68% reported that they also have their own quality assurance program. Conclusions. TDM of immunosuppressants is a recommended practice for transplant patients in Argentina. Initiatives need to be taken at the national level to develop uniform guidelines for analytical laboratories that include TDM-related quality assurance processes with regulatory force. There is also a need to train technical and professional personnel and to invite the participation of public and private organizations in the regulatory, public health, and research areas. [ABSTRACT FROM AUTHOR]

Introduction: Currently the proliferation of drugs complicates prescribing physician for proper and unerringly handled, gaining importance when the existence of the doctrine known as "Rational Prescription Drug" a discipline that leads inescapably to who makes farmacomedicación to be have this prudent and stay updated; drug interactions considering those changes on the pharmacokinetics , mechanism of action, or the effect of a drug can produce another drug, food or other substances when administered concomitantly. Objetive: Determine drug interactions in patients hospitalized in Internal Medicine, University Hospital "Dr. Angel Larralde". Materials and methods: The medical records of patients hospitalized in Internal Medicine at University Hospital were reviewed "Dr. Angel Larralde" in the June 2014 period - December 2015, being constituted the sample for the first 104 medical records that met the inclusion criteria (clinical history readable and encoded for your records), registering INFORMATION MUST in Medscape Interaction Checker application (WebMD, LLC), where drug interactions also are classified according severity and nature of each obtained explained. The results were analyzed with SPSS.20 program for Windows, using descriptive analysis techniques and statistical significance, Pearson correlation coefficient. Results: 104 stories distributed according to their age group <60 years 20% (n = 21), between 60 to 70 years 34% (n = 35) and> 70 years 46% (n = 48) with an average age of 73 were studied ± 14.3 years. It was noted that all patients showed a variability in the number of drugs used corresponding to 26% (n = 27) 2 to 5 drugs used, 55% (n = 57) 6 to 9 drugs used and 19 % (n = 20) ≥ 10 drugs used. As for drug interactions it was observed that 85.6% (n = 89) had interactions of which 44% (n = 46) had between 1 to 5 interactions, 20% (n = 21) between 6 to 10 interactions, 15% (16) 11 to 15 interactions and 6% (n = 6)> 15 interactions. Likewise 66% (69) had pharmacodynamic interactions type and 34% (n = 35) pharmacokinetic interactions (2 absorption level interactions, 2 distribution, hepatic clearance 23, 4 and 4 renal elimination unknown). The Drug Interactions by consequence was distributed with 31% (n = 32) beneficial interactions, 52% (n = 54) harmful interactions and 17% (n = 18) banal interactions; and by severity 1% (n = 1) interactions were lower, 31% (n = 32) interactions moderate, 62% (n = 65) significant interactions and 6% (n = 6) severe interactions. and the number of drugs used (r = 0.9818; P.VALUE 0.0000) with total drug interactions, by correlating variables close and significant correlation between age (P-value = 0.9972 0.0000) was evident. CONCLUSIONS: The prevalence of drug interactions was high (85.6%), predominantly in the age group > 70 years with more than 6 drug interactions in a single patient, predominating pharmacodynamic interaction type , followed by the predominant alteration farmacocinteica Hepatica elimination level and more than 50% were negative and 62% were significant interactions ; this increases with the progressive increase in the number of drugs used, where it was observed that more than 55% consumed more than 6 drugs. Hence the importance of knowledge of the fundamental bases for the prevention of drug interactions become more relevant in the Older Adult population is the group most susceptible to poliimedicacion. [ABSTRACT FROM AUTHOR]

It describes the chemical characteristics and the effects of Ayahuasca consumption, in order to know the current status of the discoveries to date regarding their pharmacological properties. A literature review was performed on studies of ayahuasca until 2013 in English, Spanish, and Portuguese in the databases of PubMed, PsycINFO, Psyke, Psicodoc, and Redalyc; as well as chapters in books and literature obtained from related research. It is concluded that one of the components of ayahuasca -- harmina -- can be used to treat different pathologies. [ABSTRACT FROM AUTHOR]

Introduction: The in vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/ effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance. [ABSTRACT FROM AUTHOR]

Attention Deficit Disorder Hyperactivity Disorder (ADHD) is one of the most common disorders in Child and Adolescent Psychiatry, and very often requires pharmacological intervention in its treatment plan. Among these, lisdexamfetamine is available in Spain since about one year ago, new both as being an amphetamine and as a prodrug. Objective: To review and summarize the evidence on lisdexamfetamine and its use in ADHD children and adolescents. Method: A comprehensive literature search in PubMed was done with the following terms: lisdexamfetamine, OR lisdexamphetamine, OR lisdexanfetamina. Results: Lisdexamfetamine is a prodrug with a safety profile similar to other known ADHD pharmacological treatments, and very effective for ADHD treatment in children and adolescents, with a low potential for abuse or misuse, and a stable clinical response extended along the day. Limitations: Although it is a drug with a known profile of efficacy and security along its nearly 9 years of marketing in the US, it should be necessary to conduct longer-term prospective studies to show more data about its safety and efficacy, efficacy related to other ADHD treatments, and its use in the real patient. [ABSTRACT FROM AUTHOR]

The monoterpenes have been reported for their important pharmacological activities such as antitumor and anti-inflammatory. The inflammatory process may be controlled, for example, by the use of cyclooxygenase inhibitors. However, despite many studies on the anti-inflammatory activity of essential oils and/or isolated monoterpenes, few studies have investigated the mechanism of action due to inhibition of enzymes involved in the inflammatory process. Given the above, this study aimed to apply in silico approaches to understand the anti-inflammatory properties of the essential oils rich in monoterpenes. For this, we selected twenty monoterpenes, common in essential oils, and performed an in silico study of the physicochemical and pharmacokinetic properties and interactions with cyclooxygenase 1 (COX-1) and 2 (COX-2) enzymes. The results suggest that these natural products have molecular characteristics and pharmacokinetic properties (including the human intestinal absorption, plasma protein binding, and blood-brain coefficient partition) suitable for bioactive substances drug candidates. The determined properties are consistent with the activities reported for monoterpene in essential and/or isolated oils. Moreover, some of the monoterpenes showed interaction with COX-1 and COX-2 enzymes, with energy and orientation similar to ibuprofen. Among the monoterpenes evaluated, the geraniol showed the greatest interaction energy with the COX - 1 and COX - 2 enzymes, being anchored in the same region of the enzyme that ibuprofen. Thus, additional in silico studies can contribute to a better understanding of the mechanism of monoterpenes with anti-inflammatory action. [ABSTRACT FROM AUTHOR]

Introduction: Good governance of resources and global warming has attracted interest on minimal flow (0.3-0.5 l/min) inhalation anesthesia. Objectives: To evaluate the predictive and clinical performance of a TCI (Target-controlled infusion) device, and its pharmacokinetic correlation for sevoflurane. Methods: Prospective, longitudinal, and analytical study on 25 adult patients. Fresh gas flow used 0.5 l/min. Target concentration of 1.2% (v/v). Continuous and variable infusion into the circuit of the anesthesia workstation. Controller developed with LABVIEW 6.1. Hemodynamic, respiratory and anesthetic depth data collected every 5 s using the anesthesia workstation software. Bias (Median of Predictive Error, MDPE%), inaccuracy (Absolute Mean of Predictive Error, MDAPE%), wobble, and divergence of the TCI device were determined in the first hour. STATA-12 pk collapse was used to analyze the area under the curve of the target and expired concentrations. The results are expressed as mean (95% CI) and median [IQR]*. Results: Target concentration used 1.22 [1.14-1.37]%*, reached in 04:07 [03:15-06:15]* min:s (expiratory branch). Anesthetic duration 1:10:50 (00:56:57-1:24: 43) h:min:s. Sevoflurane consumption 6.9 (5.7-8.0) ml. MDPE% -12.8 (-17.6 to -8.1) %; MDAPE% 15.9 (11.9-19.8) %; wobble 6.9 (5.0-8.7)% and divergence 0.89% (-5.96 to 7.7)%h-1. Interactions per hour on the TCI of 3 (2-4). Correlation of the area under the curve, Spearman's rho = 0.8577, p < 0.00001. ⩾15% inaccuracy was associated with age >65 years and obesity.Conclusions: The TCI sevoflurane© showed good performance, and the target concentration was rapidly reached and remained stable, with few interactions with the device needed during the first hour. There were neither overdosing nor clinically significant alterations. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis is a renal replacement therapy, conducted through the peritoneal membrane, which facilitates the exchange of substances between two compartments: blood and peritoneal cavity. There are drug characteristics (smallness, lipid solubility, etc.) that favor its spread, some of the peritoneum (thin thickness, etc.) and others of the dialysate (osmolarity, etc). [ABSTRACT FROM AUTHOR]

Ceftriaxone is a third generation cephalosporin widely used today. It is a drug that inhibits the synthesis of the microbial wall, possessing broad spectrum of activity against gram-negative bacteria. The purpose of this study was to conduct a literature review on the pharmacological aspects of ceftriaxone, including the mechanism of action that may explain the toxic effects and acute and longterm. Methods: For this is a review of the literature using the keywords ceftriaxone, adverse reactions, pharmacokinetics and cephalosporins through the MEDLINE and LILACS. The search includes all articles published between 1985 to 2008. Results: There are still many unanswered questions about the pharmacology of ceftriaxone and physiology of its toxic effects. A simple description of the mechanism of action is insufficient to explain all the effects of this antibiotic. Conclusion: There is little information in the literature on the pharmacology and mechanism of action of ceftriaxone that may explain its adverse effects. Further studies are needed to ensure that health professionals may obtain information and knowledge in order to combat the adverse effects resulting from treatment with ceftriaxone. [ABSTRACT FROM AUTHOR]

CIGB-300 is a synthetic peptide that inhibits the phosphorylation mediated by enzyme casein kinase 2 (CK2) and has a marked antineoplastic effect in different preclinical models. In the clinical setting, it’s explored in phase I and II studies using different routes of administration. In particular, the use of the intravenous route requires a reliable analytical method for the detection of CIGB-300 in plasma. A competitive ELISA was developed to detect and quantify the CIGB-300 peptide in human plasma samples. This system showed a detection limit of 0.030 μg/mL and a working range from 10 to 0.039 μg/mL, including concentrations achieved in plasma of patients treated with CIGB-300. In addition, the intra and inter-assay precisions were (coefficient of variation < 5%) and (CV < 17%) and the recovered range from 98.9 to 119.8%. Finally, the impact of three freeze-thaw cycles and the sample storage at - 80 °C on the stability of the analyte was evaluated. We obtained a CV < 20% for all samples in the stability study. The results support the application of this analytical method as a new tool for the pharmacokinetic studies of the early stages of clinical research with the new anti cancer drug CIGB-300. [ABSTRACT FROM AUTHOR]

Title: Pharmacodynamic and pharmacokinetic changes in critically ill patients: implications on drug treatment Drug prescription in critically ill patients involves understanding the pathophysiological changes that happen in the function and structure of organs and systems as a result of severe disease, as they may result in changes on the pharmacokinetics and pharmacodynamics. The associated comorbidities in this population, as malnutrition, obesity or aging, can also influence drug therapy. This can result in any increase in the incidence of adverse effects of the drugs or in a decrease in the pharmacological response. It justifies the necessary role of the clinical pharmacist in the intensive care unit to help physicians implementing drug therapy more effective, safe and less expensive. The aim of this paper is to review the available evidence on the pharmacology of critical patients including the main groups of drugs used in these patients and to reaffirm the role of clinical pharmacists in these units. [ABSTRACT FROM AUTHOR]