Iranian Journal of Pharmaceutical Sciences

Cefixime is a significant member of orally active third generation cephalosporin and has excellent activity against many pathogens. The virtual bioavailability of a newly industrial dispersible tablet is compared with a recognized identified formulation. An open-label, single-dose, randomized, 2-way crossover study was conducted in fasted healthy Iranian male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to be given one tablet (400 mg) of the test or reference formulation, followed by a 2-week washout period and administration of the exchange formulation. The study drugs were administered after a 10-hour overnight fast. A simple and available reversed-phase HPLC method with UV detection has been urbanized and validated for cefixime evaluation in human plasma using a C18analytical column and a mobile phase of tetrabutylammonium hydroxide (pH=6.5)-acetonitril (3:1 v/v). The detection wavelength was 280 nm. The cefixime serum concentration time curves were used to find pharmacokinetic parameters counting AUC0–24, AUC0–∞, and Cmax. In this method major linear response-concentration association all through the cefixime concentration range of 15-100 ng/ml, with the average accuracy within-run and between-run values of 97.29 and 99.27 percent, was observed. The average drug recovery from plasma was 98.2 percent throughout the linear concentration range. The limits of detection (LOD) and quantitation (LOQ) of the method were 5 and 15ng/ml, respectively. The mean (SD) Cmax, Tmax, AUC0–24, and AUC0–∞ values after administration of the test and reference formulations, respectively, were in this manner: 4.68 (0.97) versus 4.72 (0.67) μg/mL, 4.28(0.86) versus 4.25 (0.73) hours, 43.37 (1.13) versus 43.39(1.22) μg/mL/h, and 60.17 (1.98) versus 59.96 (2.13) μg/mL/h. The mean (SD) t1/2 was 5.32 (2.01) hours for the test formulation and 5.34 (2.13) hours for the reference formulation. No statistical differences were showed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90 % confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0–∞ and AUC0–24 h of cefixime were in the bioequivalence range (97 %–119 %). The method is rapid, simple, very stable and specific for the partition, assignment, pharmacokinetic and bioavailability evaluation of cefixime healthy Iranian adult male volunteers.

Prostate cancer is a devastating disease for which current therapies are inadequate. Various lines of evidences have suggested the 5-lipoxygenase (5-LOX) pathway and the leukotriene receptor pathway are potential targets for prevention or treatment of Prostate cancer. Thus, search for new anti-cancer drugs targeting 5-LOX and leukotriene is very essential and important. The objective of the present study was to evaluate the in vitro anti- cancer effects of 5-LOX inhibitor-Boswellic acid and cysteinyl leukotrienes receptor antagonist-Montelukast sodium by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay and Sulphorodamine B assay (SRB) against human prostate cancer cell line PC-3. Cell viability was assayed by trypan blue dye exclusion assay. A study was carried out in 24, 48, and 72 hours. In addition, effect of combination of both the above drugs was also determined by the same assays. Boswellic acid and Montelukast sodium demonstrated a substantial anti-cancer effect against the PC-3 cell line. The cytotoxicity of both the drugs increased with increase in duration of drug treatment. A combination of both drugs showed significant reduction in cell viability but did not show any synergistic activity. Complete dose-response curves were generated and IC50 values were calculated for all the assays. IC50 Value for Boswellic acid was found to be 49.15- 45.80 μg/ml and 50.14-43.39 μg/ml by MTT assay and SRB assay, respectively at the same time IC50 value for Montelukast sodium was 49.27-46.77 μg/ml and 46.68-46.47 μg/ml by MTT assay and SRB assay respectively. In summary, Boswellic acid and Montelukast sodium are likely to be valuable for the treatment of prostate cancer, but further studies are required for their more extensive biological evaluations.

The aim of this study is to assess cost-effectiveness of infliximab, compared with conventional treatments in patients with moderate to severe Ulcerative Colitis (UC) in Iran. We developed an analytical decision model with a 5-year-time horizon to follow up 1000 hypothetical patients, in order to estimate treatment costs and outcomes. Hypothetical patients were individuals with moderate to severe UC that are resistant to conventional treatments. Remission rate, clinical response, and surgery were selected as clinical outcomes. For estimating QALY, utility value related to each state, was derived form published paper. We also estimated associated probabilities by using patients ’medical records and specialists’ opinion. Costs of treatment such as Physician visit fee, laboratory tests, hospitalizations, surgery, and drugs were estimated based on the public sector tariffs and drug price list set by pricing committee of food and drug administration. Infliximab costs at dosage of 5 mg /kg were considered for UC patients with average weight of 75 kilogram. Incremental Cost-Effectiveness Ratio (ICER) of infliximab treatment in UC patients were 240,903 USD dollars per QALY gained, compared with conventional treatments. According to recommendation of World Health Organization for choosing cost-effective intervention, interventions with relative cost-effectiveness value less than 3 times of Gross Domestic Production (GDP) per capita, are cost–effective. Our result showed that the ICER value of infliximab is approximately 51 times of Iran’s local GDP per capita, in 2014 – i.e. more than 3 time GDP per capita. Thus, for UC patients, our finding indicates that infliximab is not a cost- effective treatment.

One of the main components of the stress system is hypothalamus- pituitary-adrenal (HPA) axis. Acute activation of μ-opioid receptors increases the activity of the HPA axis, leading to release of ACTH and corticosterone. Glucocorticoids can change behaviors, depend on age but there were no evidences about the interaction between age, opioid system and glucocorticoids. In this experiment, effects of dexamethasone (1mg/kg) and RU486 (20mg/kg) as an agonist and antagonist of glucocorticoid receptors, morphine (5mg/kg) and naloxone (20mg/kg) as an agonist and antagonist of the opioid system on anxiety in young and adult male Wistar rats were examined. The percentage of time in the open arms of plus maze was evaluated for anxiety behavior also percentage of the number of entries in closed arms was evaluated for locomotor activity. The results showed that morphine (5mg/kg) and dexamethasone (1mg/kg) had an anxiolytic effect on both young and adult rats while just in young rats reduced locomotor activity. RU486 could prevent the anxiolytic effect of morphine, and the anxiolytic effect of dexamethasone had been inhibited by naloxone in young but it wasn't seen in adult rats. These results show an interactive effect between glucocorticoids and the opioid system on mediating anxiety that can be influenced by age.

Olea europaea L. commonly known as olive has been traditionally used for the prevention and treatment of many diseases since ancient times. Olive has been reported to possess a broad spectrum of pharmacological properties. In the present study, we investigated the activity of aqueous extract of Olea europaea L. fruit at various concentrations on A2780, A172, and HFFF2 cell lines proliferation by MTT assay. Aqueous extract of olive significantly increased cell proliferation in a dose dependent manner in the cell lines. It has been previously reported that olive has chemoproventive and anti-tumor effects. These disagreements can be explained by differences in cell line properties, type of olive and different solvents in the extracts. However, further investigation is needed to clarify the exact role of olive in cell proliferation and cancer. In this study fruit extract of Olea europaea L. showed more activatory effects on A2780 cell line in comparison with A172 and HFFF2. These differences in the activatory effects may be related to the activation of different signaling pathways in different cell lines.

The aim of the present study was to provide a clear picture of the prescribing pattern of corticosteroids in Zanjan, Iran. A retrospective and cross-sectional study was conducted to describe the pattern of corticosteroids prescription at Beheshti pharmacy (Zanjan, Iran) over a period of six months between March 21 and September 22, 2013. Descriptive analyses were stratified by gender, age, type of prescribed corticosteroid and rout of administration. Separate analyses were performed to determine the most common indications leading to the prescription of injection dexamethasone. Corticosteroids were prescribed mostly (74.56%) as injection. The overall corticosteroid prescribing rate was 25.73%; 55.86%, and 44.14% in females and males, respectively. Corticosteroids were prescribed frequently for adults in both males and females. In young and middle-aged women, corticosteroids were prescribed substantially higher than in men of the same age. Dexamethasone as the most prescribed corticosteroid in both male and females was mostly prescribed for respiratory bacterial infections. The current study grows the knowledge about the use of corticosteroids in Iran and suggests more attempts to reduce corticosteroids prescription. Educational interventions to promote hygiene in the society could improve rational use of corticosteroids.

Common Hawthorn has been known as a traditional remedy to relieve gastroesophageal reflux disease symptoms and to improve stomach function. This study aims to investigate the effectiveness and safety of common hawthorn fruit in patients who suffer from gastroesophageal reflux disease.Eighty male and female patients with clinically diagnosed gastroesophageal reflux disease were included in the study. The patients were randomly assigned into experimental (treatment) and control groups. Experimental group members took common hawthorn syrup and those in the control group received placebo syrup for 4 weeks (5 ml after each meal). Gastroesophageal reflux disease symptoms were assessed based on an available validated questionnaire, before and after the treatment in both groups. The side effects were monitored according to old and new medical resources. In order to assess the probable effect on hepatic or renal function, the levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, and creatinine were measured before and after the treatment.After four weeks of taking the hawthorn and placebo syrups, a significant improvement was observed in two main symptoms of gastroesophageal reflux disease in the experimental group compared with the control one. Heartburn and regurgitation were alleviated by 93.5% and 94.2% respectively. The impact of the common hawthorn syrup on atypical symptoms of gastroesophageal reflux disease such as dyspnea, chest pain, cough and dysphagia was also evaluated and differences were not statically significant. Any adverse effects of the medicine on the functions of liver and kidney were not observed. Our findings suggest common hawthorn fruit as a natural source to control the main symptoms of gastroesophageal reflux disease.

Incorporation of functional foods and nutraceuticals such as carotenoids which suffer from poor water solubility and low bioavailability into nano-sized delivery systems can improve their solubility, stability, and oral bioavailability. The aim of this study was to prepare β-Carotene nanodispersion and investigate the effects of preparation parameters by means of response surface methodology using central composite design. Therefore, the impact of the preparation conditions namely the homogenizer speed, evaporation temperature, and rotation speed (as independent variables) on the mean particle size, particle size distribution, and β-carotene amount of the prepared β-carotene nanodispersion (as responses) were evaluated. A multiple-optimization procedure showed that the optimum conditions of homogenization speed as well as evaporation temperature and rotary speed were 15000 rpm, 32 °C , and 140 rpm, respectively. A statistical assessment showed insignificant (p > 0.05) differences between experimental and predicted responses values, verifying the fitness of the final reduced models for explaining the variation of nanoemulsion properties. Using statistical methods can reduce the number of experiments by optimizing of formulations during development and lead to significant save in time and cost.