BackgroundIt is still controversial whether pomegranate causes drug interactions. Pomegranate juice has been shown to inhibit CYP3A in-vitro and animal studies. The co-administration of pomegranate juice with cyclosporine, a narrow therapeutic drug that is the substrate of CYP3A, might lead to drug toxicity. The objective of this study is to investigate the effect of pomegranate juice on the pharmacokinetics of cyclosporine in healthy Thai volunteers.MethodsThe study design was an open-label, randomized, single dose, crossover study with a 2-week washout period. Each fasting subject received 2 microemulsion tablets of 100 mg of cyclosporine with 500 ml of pomegranate juice (test) or 500 ml of water (control). Serial blood samples were collected up to 24 h after dosing, and blood samples were analyzed for cyclosporine concentrations by using chemiluminescent microparticle immunoassay. Fourteen healthy volunteers completed the study.ResultsThe 90% confidence intervals for the test/control ratio using logarithmically transformed data of area under the concentration-time curve (AUC) from time zero until the last measured concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), and maximum concentration (Cmax) were 91.6-105.6, 92.0-105.2 and 82.3-102.5, respectively. The results were within the accepted bioequivalence range for narrow therapeutic index drugs (90-111% for AUC and 80-125% for Cmax). There were no differences in adverse event between the groups.ConclusionSingle dose administration of pomegranate juice with cyclosporine did not significantly affect the oral bioavailability of cyclosporine. However, further work is needed to thoroughly evaluate the effect of pomegranate on narrow therapeutic drugs.

Background 2-iminobiotin (2-IB) is an investigational neuroprotective agent in development for the reduction of brain cell injury after cerebral hypoxia-ischemia.Objective The present first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK) and -dynamics (PD) of 2-IB in healthy male subjects, intravenously infused with or without Captisol® as a solubilizing agent.Methods This randomized, double-blind, placebo-controlled, dose-escalation study was executed in 2 groups of 9 healthy male subjects. A single dose of 2-IB 0.6 mg/kg or placebo was infused over periods between 15 min and 4 h, and repeated doses escalating from 0.6 mg/kg to 12 mg/kg, or placebo were infused every 4 h for 6 administrations in total.Results Single and multiple doses of 2-IB up to 6 doses of 6 mg/kg with and without Captisol® were safe and well-tolerated in healthy male subjects. 2-IB proved to be a high-clearance drug with a volume of distribution slightly exceeding total body water volume, and with linear PK that appeared not to be affected by the presence of Captisol®.Conclusion Sulfobutyletherbeta-cyclodextrin (SBECD) in Captisol® had a low-clearance profile with a small volume of distribution, with time-independent PK. Preliminary PD characterization of repeated iv dosing of 2-IB in an acute peripheral hypoxic ischemia model in healthy subjects did not reveal any notable effects of 2-IB, noting that this model was not selected to guide efficacy in the currently pursued indication of cerebral hypoxia-ischemia.

Objective: We aimed to determine the therapeutic drug monitoring (TDM) features and the relation to Brain-Derived Neurotrophic Factor (BDNF) of frequently used new antiepileptic drugs (NADs) including lamotrigine (LTG), oxcarbazepine (OXC), zonisamide (ZNS) and lacosamide (LCM). Moreover, we investigated their effect on the quality of life (QoL).Methods: Eighty epileptic patients who had been using the NADs, and thirteen healthy participants were included in this cross-sectional study. The participants were randomized into groups. The QOLIE-31 test was used for the assessment of QoL. We also prepared and applied “Safety Test”. HPLC method for TDM, and ELISA method for BDNF measurements were used consecutively.Results: In comparison to healthy participants, epileptic participants had lower marriage rate (p=0.049), education level (p˂0.001), alcohol use (p=0.002). BDNF levels were higher in patients with focal epilepsy (p=0.013) and in those with higher education level (p=0.016). There were negative correlations between serum BDNF levels and serum ZNS levels (p=0.042) with LTG-polytherapy, serum MHD levels (a 10-monohydroxy derivative of OXC, p=0.041) with OXC-monotherapy. There was no difference in BDNF according to monotherapy-polytherapy, drug-resistant groups, regarding seizure frequency. There was a positive correlation between total health status and QoL (p˂0.001). QOLIE-31 overall score (OS) was higher in those with OXC-monotherapy (76.5±14.5). OS (p˂0.001), seizure worry (SW, p=0.004), cognition (C, p˂0.001), social function (SF, p˂0.001) were different in the main groups. Forgetfulness was the most common unwanted effect.Conclusion: While TDM helps the clinician to use more effective and safe NADs, BDNF may assist in TDM for reaching the therapeutic target in epilepsy.

BackgroundBenzodiazepine is one of the most important causes of substance abuse and intoxication throughout the world and Iran.ObjectiveThe aim of our study is to determine the role of stimulants in reversing CNS level in acute Benzodiazepine poisoning patients who were hospitalized at referral poison center.MethodThis was a randomized double-blind placebo-controlled trial study on 32 cases with pure acute Benzodiazepine poisoning from March 2016 to February 2017. Diagnosis of pure acute poisoning was based on history, and laboratory confirmation. We gathered the demographics, clinical data, laboratory data, hospitalization and outcome. Participants were randomized into two groups: Methylphenidate Group (MPH) and Placebo Group (PBO).ResultsThe randomized sample consisted of 32 participants who were predominately female (83%). The majority of the PBO group and the MPH group reported improvement in their consciousness with a significant difference between the two groups (p = .005). Paired sample t-test analyses on Reed Scale data revealed an increase in the probability of improvement during the trial for the MPH group compared to the PBO group. Furthermore, the HCo3 (bicarbonate) level has a significant p-value with respect to age groups (p = .02). None of our cases required either the ICU facility or intubation.ConclusionOur study provided the MPH superiority over PBO in reversing CNS symptoms in loss of consciousness in acute BZD poisoned patients. Thus, this trial provides concrete evidence that improvement in consciousness levels (Reed Scale rated) among those patients receiving MPH was associated with a methylphenidate use.

BackgroundHeart failure is a common medical problem in the world, which has a high prevalence in both developed and developing countries. Today, among the medications used for the heart failure treatment, there are many medications with a positive cardiac contraction effect (positive inotropic such as digital glycosides, adrenergic receptor stimulants, and phosphodiesterase inhibitors), a large number of cardiac diluents (such as Angiotensin-Converting Enzyme (ACE) inhibitor group), and a few other types of drugs whose final effects are still under review. Statins are valuable drugs that are broadly prescribed in hyperlipidemia and cardiovascular patients due to their multiple properties, such as cholesterol reduction, endothelial function improvement, anti-oxidative, anti-inflammatory, neovascularization, and immunomodulatory activities.MethodsThere is evidence that the therapeutic role of statins in HF, due to myocardial hypertrophy, show reduction in cardiomyocyte loss in the apoptosis process, oxidative stress, inflammation, and also the return of neurohormonal imbalance. However, the fact that these drugs have no side-effects has not been confirmed in all studies, as statins prevent the production of particular beneficial and protective factors, such as coenzyme Q10 (CoQ10), while inhibiting the production of specific proteins involved in pathologic mechanisms.ResultsRecently, it has been hypothesized that, despite the positive effects reported, high doses of statins in patients with long-term heart failure lead to progress in heart failure by inhibiting CoQ10 synthesis and intensifying hypertrophy.ConclusionThus, it can be stated that the advantage of using statins depends on factors, such as stroke fraction, and the existence of other standard indications such as atherosclerotic diseases or high Low-Density Lipoprotein-C (LDL-C).

Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.

Poor adherence to the prescribed therapy leads to low bone mineral density and enhance the development of osteoporosis complications and unnecessary hospitalization. To explore factors associated with medication non-adherence in patients with osteoporosis. Findings would help guide the development of future pharmaceutical care interventions aim at improving health outcomes for patients with osteoporosis. The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services Hospital. Variables including socio-demographics and medical factors were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop a model with variables that best predicted medication non-adherence in patients with osteoporosis in Jordan. A total of 296 patients participated in the study. Most of the study participants (72.3%) were found non-adherent. Patients were found less likely to adhere to the prescribed medications with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680) and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058). Medication adherence for patients with osteoporosis has considered scope for improvement in Jordan. Simplifying dosage regimen in addition to taking patients' preferences when selecting the medications should be taken into account in future interventions designed to improve health outcomes for patients with osteoporosis.