ABSTRACT
ABSTRACT The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.
ABSTRACT
Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the "Interchangeable Pharmaceutical Product in the Treatment of Epilepsies" questionnaire was applied. The questionnaires "Adverse Events Profile" and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event "problems with skin" incresead (p=0.023) and "upset stomach" decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: "energy/fatigue" (p=0.048) and "total score" (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients' perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients' life.
Subject(s)
Humans , Male , Female , Adult , Patients/classification , Carbamazepine/adverse effects , Drugs, Generic/analysis , Epilepsy/pathology , Interchange of Drugs , Anticonvulsants/analysisABSTRACT
Até o ano de 1940, as doenças infecciosas eram uma das principais causas de morte no Brasil. Atualmente, apesar de um grande declínio, a mortalidade ainda é elevada em relação a países desenvolvidos e a outros países da América Latina. Dessa maneira, o objetivo do presente trabalho foi relatar as alterações fisiológicas em condições específicas, as consequências na farmacocinética dos antimicrobianos e ainda o impacto do ajuste de dose em tais situações. Realizou-se uma revisão narrativa de artigos publicados sobre a utilização de antimicrobianos nas seguintes situações: doença crítica e sepse, alcoolismo, tabagismo, extremos de idade, obesidade, nutrientes, polimorfismo genético, gravidez e lactação, insuficiência cardíaca, insuficiência hepática e renal. Observou-se que as alterações fisiológicas em tais situações afetam a farmacocinética dos antimicrobianos, modificando os processos de absorção, distribuição, metabolismo e excreção, os quais dependem muitas vezes da natureza do fármaco, podendo requerer ajuste de dose. Pôde-se concluir que as alterações observadas reduzem a precisão de uma dose terapêutica eficaz, evidenciando, dessa maneira, a importância do ajuste de dose.
Until the year 1940, infectious diseases were one of the main causes of death in Brazil. Currently, despite a large decline, mortality is still high in comparison to developed countries and other Latin American countries. Thus, the objective of the present study was to report the physiological changes under specific conditions, the consequences on the pharmacokinetics of antimicrobials and also the impact of the dose adjustment in such situations. A review of published articles on the use of antimicrobials was conducted in the following situations: critical illness and sepsis, alcoholism, smoking, age extremes, obesity, nutrients, genetic polymorphism, pregnancy and lactation, heart failure, hepatic and renal failure. It has been observed that the physiological changes in such situations affect the pharmacokinetics of antimicrobials, modifying the absorption, distribution, metabolism and excretion processes, and which often depend on the nature of the drug, which may require dose adjustment. It could be concluded that the observed changes reduce the accuracy of an effective therapeutic dose, thus evidencing the importance of the dose adjustment.