Audrius Sveikata

Comparison of the pharmacokinetic and pharmacodynamic properties of two recombinant granulocyte colony-stimulating factor formulations after single subcutaneous administration to healthy volunteers

BACKGROUND AND OBJECTIVE The aim of this randomized, single dose, two-period crossover study with two weeks wash-out period was the demonstration of bioequivalence of two recombinant human granulocyte colony-stimulating factor (rG-CSF) formulations after subcutaneous administration of 300μg comparing their pharmacokinetic (primary endpoints AUC0-24, AUC0-∞ and Cmax) and pharmacodynamic (primary endpoints ANC AUC0-72, ANC AUC0-∞ and ANCmax) profiles in healthy male subjects. MATERIALS AND METHODS A total of 36 (23.0±6.0 years, 76.6±7.2kg) healthy subjects were recruited. Using a 1:1 randomization ratio, subjects were randomly assigned to one of two possible treatment-sequence groups to receive the single dose of test formulation (Gp-02) and reference product (Neupogen™) concentrations were measured by enzyme-linked immunosorbent assay (ELISA) up to 24h and the Absolute Neutrophil Count (ANC) was determined using hematology analyzer Coulter STKS™ (Beckman Coulter) up to 72h after injection. The geometric mean of primary pharmacokinetic and pharmacodynamic variables were considered bioequivalent if the 90% confidence intervals (CI) would fall in the bioequivalence range of 80%-125%. RESULTS AUC0-24 (ratio of means 103.4, 90% CI: 95.6-111.9), AUC0-∞ (103.4, 90% CI: 95.7-111.7), Cmax (99.6, 90% CI: 89.0-111.4), ANC AUC0-72 (100.0, 90% CI: 96.6-103.5), ANC AUC0-∞ (100.8, 90% CI: 96.5-105.3), and ANCmax (100.2, 90% CI: 95.4-105.1) were determined. Single doses of test and reference formulations were well tolerated. The incidence of AEs was equally distributed across treatment groups with the most frequent AEs being headache, fever, and back pain. CONCLUSIONS The study results demonstrated the bioequivalence of Gp-02, a new formulation of filgrastim, and the reference product Neupogen™.

The prevalence of metabolic risk factors among outpatients with diagnosed nonalcoholic fatty liver disease in Lithuania.

Summary Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease; there is growing evidence that it is a hepatic manifestation of a metabolic syndrome. This study aimed to assess the prevalence of metabolic risk factors among patients with NAFLD. Material/Methods Outpatients with NAFLD were recruited into the study. Family physicians recorded patients’ demographic and anthropometric data, leisure-time physical activity, concomitant diseases, and pharmacological treatment for NAFLD into standardized Case Report Forms. Results In total, data on 798 patients were analyzed. Most patients were women and they were older than the men (mean age, 60.2±9.6 vs. 54.5±11.4 years; p<0.05). Metabolic risk factors (obesity, arterial hypertension, dyslipidemia) were highly prevalent in the study patients, and these factors were more prevalent among women. There were no differences in the mean Body Mass Index (BMI), in the proportion of men or women with BMI >30 kg/m2 or central obesity in the 2 age groups (≤60 years and >60 years). Hypertension and diabetes were more prevalent among older men and women. Dyslipidemia was more common among older women. The level of leisure-time physical activity was lower in women and in older patients. The most frequently prescribed pharmacological agents were cytoprotective agents, lipid-lowering drugs, and antioxidants. Conclusions Metabolic risk factors were highly prevalent among patients with NAFLD. Obesity, hypertension, and dyslipidemia were more prevalent among women. The differences in the prevalence of hypertension seemed to be influenced by older age of women.

Drug Induced Agranulocytosis: a Case Report

Agranulocytosis may cause life-threatening infection and death, therefore prompt diagnosis and appropriate treatment are crucial. We report the case of severe agranulocytosis which occurred in 20 years woman who used tiamazol. The clinical manifestation of agranulocytosis was febrile neutropenia and systemic inflammatory reaction syndrome with multiple organs dysfunction. Following the appropriate treatment, including administration of filgrastim, and withdraw of the suspected medicinal product, agranulocytosis disappeared and the patient was discharged from the hospital. Article in Lithuanian. doi:10.5200/sm-hs.2012.079