Evaluation of Safety and Pharmacokinetic Behavior of Unipeg® in Healthy Human Volunteers – Pages 220-227

Evaluation of Safety and Pharmacokinetic Behavior of Unipeg® in Healthy Human Volunteers
Pages 220-227
T. Ahmad, R. Ahsan, M.R. Raza and G. Saba
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.8
Published: 25 August 2014

Abstract: Peginterferon α-2a (20kDa) derived from Hansenula Polymorpha is a distinct variety of peginterferons (PEG-IFN). A pilot study of this drug was conducted on healthy human subjects to evaluate its safety and pharmacokinetic behavior in local population.

With due approval of the IEC operating under ICH-GCP guidelines; ten healthy male subjects were selected randomly from the Pakistani population after thorough screening and signing of the Informed consent for an open label, single dose study.Each subject received a subcutaneous injection of the drug (180µg) in abdominal skin and blood samples were collected at 0 and 1, 2, 3, 6, 12, 24, 36, 60, 84, 108, 132 and 156 hours, andanalyzed by a validated ELISA method for peginterferon α-2a (20kDa), Unipeg®.

The Mean ± SEM (standard error of mean) PK parameters were found to be: Cmax: 18.67±2.92 ng/ml (7.05-34.51); AUC0-∞: 1440±113 h.µg/l] (969-2101); Absorption Half-Life: 17.02±2.06 h (10.37-29.26), elimination half life: 41.437±6.21 h (18.51-78.97 h); volume of distribution 8.933±1.72 L (4.81-18.34), clearance: 112.6±8.21 ml/h (71.96–155.96).

The safety of the drug was evaluated by observation of adverse effects and evaluating the change in general health parameters, hematological and biochemical test results during and after the study.

No Sever Adverse Effect was observed however the most common adverse event (AE) was the fever; observed in all volunteers (n=10), headache (6), Fatigue (5), Vomiting (4) and diarrhea, loss of appetite, body ache was observed in 3 volunteers. Three out of ten volunteers demonstrated decrease in WBC and platelets count. Changes observed in hematology returned to normal values within 16 days.

The safety profile of UNIPEG® was found to be very similar to those of reported in literature for unmodified IFNs and other pegylated interferons generally used in therapy. Future clinical trials are recommended to further establish the safety profile and pharmacokinetics.

Keywords: PEG-IFN-α-2a, 20-kDa, Unipeg, Peginterferon alfa-2a, pharmacokinetics, clinical trial, safety.

Doctor of Pharmacy in Jordan: Students’ Career Choices, Perceptions and Expectations – Pages 213-219

Doctor of Pharmacy in Jordan: Students’ Career Choices, Perceptions and Expectations
Pages 213-219
Nadine N. Abdelhadi, Mayyada Wazaify, Feras W. Darwish Elhajji and Iman A. Basheti
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.7
Published: 12 August 2014

Abstract: Purpose: To explore Jordanian Pharm.D students’ career choices, perceptions and expectations.

Methods: This observational study was conducted during June 2013 at the University of Jordan. A total of 192 undergraduate Pharm.D students were invited to complete a questionnaire prepared and validated by the research team. The questionnaire investigated student’s demographics, the reasons behind choosing to study Pharm.D, satisfaction with the Pharm.D course, student’s future plans following graduation, and student’s perceptions about the Pharm.D specialty. Data collected were encoded and analyzed by SPSS database for Windows version17.

Results:The majority (93%) of respondents was females,aspired to work as hospital clinical pharmacists (83%) and many (68%) believed that Pharm.D graduates are well respected by the general public. Results indicated that students are unaware of the current Pharm.D salaries and have higher expectations than what is being currently offered in the country.

Conclusions:A generation of Pharm.D students from Jordan reported a future aspiration to work as hospital clinical pharmacists. Students have unrealistic salary expectations compared with the current salaries offered in Jordan. ‘Awareness workshops’ targeting students’ knowledge about the Pharm.D degree is required.

Keywords: Beliefs, Career Goals, Clinical Pharmacy, Education, Jordan, Pharm.D students.

Immunomodulatory Effects of Lycii Radicis Cortex Water Extract on Lipopolysaccharide-Activated RAW 264.7 Mouse Macrophages – Pages 207-212

Immunomodulatory Effects of Lycii Radicis Cortex Water Extract on Lipopolysaccharide-Activated RAW 264.7 Mouse Macrophages
Pages 207-212
Wansu Park
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.6
Published: 12 August 2014

Abstract: The rootbark ofLycium chinenseMiller (Solanaceae), also known as Lycii radicis cortex, is one of famous plant-originated drugs in Korean medicine owing to its anti-tussive, anti-asthmatic, and antipyretic propertiesIn thisstudy, the effect of Lycii radicis cortex water extract (LRC; 10 – 200 μg/mL) on inflammatory mediators from lipopolysaccharide (LPS)-activated RAW 264.7 mouse macrophages was inspected. After 24 h incubation with LRC, cell viability, nitric oxide (NO), and various cytokines from RAW 264.7were measured. LRC increased the cell viability of RAW 264.7 at concentrations of up to 200 μg/mL. LRC significantly inhibited the production of NO, granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-α (TNF-α), platelet derived growth factor-BB (PDGF-BB), interleukin (IL)-2, and IL-10 in LPS-activated RAW 264.7 (P < 0.05). As well, LRC diminished the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide-induced CXC chemokine (LIX). The current results suggest that LRC hasimmunomodulatory property to alleviate excessive immune reactions during the activation of macrophages by LPS.

Keywords: Lycii radicis, immunomodulatory, macrophage, cytokine, nitric oxide.

Lactic-Acid Bacteria Supplement Fermented Dairy Products with Human Behavior-Modifying Neuroactive Compounds – Pages 199-206

Lactic-Acid Bacteria Supplement Fermented Dairy Products with Human Behavior-Modifying Neuroactive Compounds
Pages 199-206
Alexander V. Oleskin, Olga G. Zhilenkova, Boris A. Shenderov, Adelaide M. Amerhanova, Vladimir S. Kudrin and Peter M. Klodt
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.5
Published: 12 August 2014

Abstract: Using high performance liquid chromatography, we established that probiotic Lactobacillus strains (Lactobacillus helveticus 100ash, L. helveticus NK-1, L. casei K3III24, and L. delbrueckii subsp. bulgaricus) grown on two milk-containing nutrient media produce important neuromediators such as biogenic amines, their precursors and deamination products, as well as neuroactive amino acids. The concentrations of biogenic amines (such as catecholamines and, with L. helveticus 100ash, also serotonin) equal or exceed those contained in the bloodstream of healthy adult humans, whereas those of most amino acids are comparatively low, except for gamma-aminobutyric acid (GABA). Of paramount importance is the fact that the bacterial cultures can release micromolar amounts of GABA and L-3,4-dihydroxyphenylalanine (DOPA)into the milk-containing media. It is known that DOPA passes through the gut-blood and the blood-brain barrier and converts into major neurotransmitters (dopamine and norepinephrine) that influence important aspects of human behavior. The data obtained suggest that dairy products fermented by live lactobacilli-containing starters are potential sources of human behavior-modifying substances.

Keywords: Microbial endocrinology,fermented dairyproducts, probiotic lactobacilli, Lactobacillus helveticusLactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, neuromediators, catecholamines, neuroactive amino acids, behavior modification, aggressiveness, dominance, biopolitics.

Nutritional and Functional Properties of Edible Mushrooms: A Food with Promising Health Claims – Pages 187-198

Nutritional and Functional Properties of Edible Mushrooms: A Food with Promising Health Claims
Pages 187-198
Viviana Loria-Kohen, Thais Lourenço-Nogueira, Isabel Espinosa-Salinas, Francisco R. Marín, Cristina Soler-Rivas and Ana Ramirez de Molina
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.4
Published: 12 August 2014

Abstract: Over the past two decades, there has been a steady flow of publications about the health effects related to mushrooms consumption. They represent a valuable source of protein, present high levels of fiber, some vitamins and minerals, and they also have reduced amount of fat and sodium. In addition, their complex carbohydrates profile can strengthen considerably the immune system.

Edible mushrooms have been related to significant functional properties due to their bioactive compounds, such as eritadenine, phenolic compounds, sterols (as ergosterol), chitosan, etc., These substances are considered as important agents in the prevention and treatment of different health conditions like obesity, diabetes, or cardiovascular disease. However, it is important to remember that most of scientific studies are made in animal models and, therefore, some evidences regarding mushroom consumption have yet to be confirmed in clinical trials.

Despite of the growing appeal for humans by their medicinal effects and nutritional value, mushrooms are also very appreciated for their texture, flavor, and versatility in culinary. They can be easily incorporated into any kind of dish, improving the dietary diversity without adding many calories.

The information presented in this review point out that the positive effect of mushrooms on health is beyond basic nutrition. Therefore, it is very valuable expanding our knowledge about mushrooms, in order to identify all their active principles and the mechanisms involved in each health benefit, getting aware about the doses required to achieve that, in a safe range for humans.

Keywords: Mushroom, functional food, disease prevention, antioxidant, umami.

In Vitro Cytotoxic Activity of Isostichopus badionotus, a Sea Cucumber from Yucatan Peninsula Coast – Pages 183-186

In Vitro Cytotoxic Activity of Isostichopus badionotus, a Sea Cucumber from Yucatan Peninsula Coast
Pages 183-186
Aida R. Pérez-Espadas, María J. Verde-Star, Catalina Rivas-Morales, Azucena Oranday-Cárdenas, María E. Morales-Rubio, Lorena V. León-Deniz, Jaqueline Canul-Canché and Leovigildo Quijano
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.3
Published: 12 August 2014

Abstract: The in vitro cytotoxic activity of hexane, ethyl acetate and butanol extracts of the sea-cucumber Isostichopus badionotus (Holothuroidea) was tested against normal cells (Vero), human cervical carcinoma (HeLa) and breast adenocarcinoma (MCF-7 andMDA-MB-231) ATCC cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.Hexane extracts from body walls and viscera showed high cytotoxic activity against HeLa cells (IC50’s = 48.5 and 42.5 µg mL-1, respectively), while the ethyl acetate extract of body walls was considered low active (IC50 = 98.3μg mL-1). In addition, the body walls hexane extract showed a good selectivity index value of 12.0.

Keywords: Holothurian, organic extracts, selectivity index, HeLa cells.

Anthropometric Characteristics and other Dietary Aspects of a Group of Spanish Women Looking for Weight Loss and Enrolled in a Weight Management Program – Pages 177-182

Anthropometric Characteristics and other Dietary Aspects of a Group of Spanish Women Looking for Weight Loss and Enrolled in a Weight Management Program
Pages 177-182
Magdalena Rafecas, Laura-Isabel Arranz, Mireia García, Miguel-Ángel Canela and DIECA group
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.2
Published: 12 August 2014

Abstract: Overweight is a health problem characterised as a higher than normal body weight due to an abnormal increase in body fat. Body weight adequacy is categorised using body mass index (BMI), however other parameters as fat mass (FM), waist circumference or waist to hip ratio, are relevant. Ideally, body composition should be calculated initially to evaluate changes during a dietary intervention for weight loss. Hunger experience is another parameter to take into account in order to succeed. The aim was to investigate and describe the characteristics of women seeking weight loss solutions. We organised an open program for people with body excess who wanted to lose weight. 252 women participated and answered to a dietary interview. Anthropometric measures of weight, height, body mass index, body fat, waist and hip circumference were taken. The mean age was of 36.84±7.29 years, and most of them, about 90%, have followed dietary programs for weight loss throughout their lives. They all wanted to lose weight in a range of 3 to 20 kilograms with a mean value of 11.49±6.01 kilograms. 123 women had a hunger profile of satiating behaviour and 129 a snacking one. The mean BMI was within overweight values, and mean fat mass was within obesity values. Waist and hip circumference were higher than normal in most of the participants and excess body weight perception and attitude were different. There is a need to tackle overweight and obesity individually, taking into account personal consciousness and expectancy, anthropometric measures and hunger experience.

Keywords: Overweight, body mass index, fat mass, waist, hip, hunger, satiety.

Adalimumab and Etanercept in the Treatment of Rheumatoid Arthritis and Spondyloarthropathies: Budget Impact Model of Dose Reduction – Pages 170-176

Adalimumab and Etanercept in the Treatment of Rheumatoid Arthritis and Spondyloarthropathies: Budget Impact Model of Dose Reduction
Pages 170-176
Alejandro González Álvarez, Manuel Gómez Barrera, Joaquín Borrás Blasco and Emilio José Giner Serret
DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.1
Published: 12 August 2014

Abstract: Objective:To assess the financial impact ofspacing out the administration intervals of adalimumab (ADA) and etanercept (ETN) in the treatment of rheumatoid arthritis (RA) and spondyloarthropathies (SAP) in our work setting.

Materials and method:A budget impact model (BIM) was developed to estimate the financial impact ofspacing out the usual administration intervals of ADA 40 mg every 2 weeks and ETN 50 mg weekly (scenario A) to ADA 40 mg every 3 weeks and ETN 50 mg every 2 weeks (scenario B), according to the guidelines and recommendations applied to these studies, specifying the target population, the study perspective, the time frame, and analysing the robustness of the study with a threshold univariate sensitivity analysis.

Results:A total of 71 patients were included in the study.The application of a BIM showed annual savings for ADA and ETN of €19,784 and €38,271, respectively.The net cost, that is, the savings this entailed for the time frame considered (2 years), amounted to €116,110.The sensitivity analysis performed shows that the BIM estimated for the study period was very robust, as the net result in the different scenarios varied very little, remaining negative in the new scenarios.

Conclusions:The BIM developed in the study shows the importance of the role of healthcare professionals in the context of sustainability of the healthcare system, where the model could generate large annual net savings for the different regional healthcare systems.

Keywords: Rheumatoid arthritis, Spondyloarthropathies, Budget impact analysis, Adalimumab, Etanercept, Tumour necrosis factor alpha inhibitors.