Oral Preparations Research Articles

Endoscopic management of delayed bleeding after polypectomy of small colorectal polyps: two or more clips may be safe.

BackgroundThe resection of small colorectal polyps (≤10 mm) is routine for endoscopists. However, the management of one of its main complications, namely delayed (within 14 days) postpolypectomy bleeding (DPPB), has not been clearly demonstrated. We aimed to assess the role of coloscopy in the management of DPPB from small colorectal polyps and identify the associated factors for initial hemostatic success.MethodsWe conducted a retrospective study of 69 patients who developed DPPB after the removal of colorectal polyps of ≤10 mm and underwent hemostatic colonoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2013 and June 2021. Demographics, clinical variables, and colonoscopic features were collected independently. We applied univariate and multivariate analyses to assess factors associated with initial hemostatic success.ResultsGeneral colonoscopy without oral bowel preparation was successfully performed in all the patients, with a median duration of 23.9 (12.5–37.9) minutes. Among 69 patients, 62 (89.9%) achieved hemostasis after initial hemostatic colonoscopy and 7 (10.1%) rebled 2.7 ± 1.1 days after initial colonoscopic hemostasis and had rebleeding successfully controlled by one additional colonoscopy. No colonoscopy-related adverse events occurred. Multivariate analysis showed that management with at least two clips was the only independent prognostic factor for initial hemostatic success (odds ratio, 0.17; 95% confidence interval, 0.03–0.91; P = 0.04). All the patients who had at least two clips placed at the initial hemostatic colonoscopy required no further hemostatic intervention.ConclusionsColonoscopy is a safe, effective, and not too time-consuming approach for the management of patients with DPPB of small colorectal polyps and management with the placement of at least two hemoclips may be beneficial.

Bicalutamide improves minoxidil-induced hypertrichosis in female pattern hair loss: A retrospective review of 35 patients

Bicalutamide improves minoxidil-induced hypertrichosis in female pattern hair loss: A retrospective review of 35 patients

Study of the compatibility of oral magnesium oxide preparations sold in Japan with the ICH-Q3D guideline for elemental impurities.

Magnesium oxide has been widely used as an antacid and constipation remedy. Currently in Japan, magnesium oxide preparations manufactured by five medical companies are marketed as prescribed generic drugs. In this study, we focused on metal elemental impurities present in 330 mg magnesium oxide tablets manufactured by each of these companies. The content of such impurities was determined by atomic absorption spectrometry and inductively coupled plasma mass spectrometry. We confirmed whether the content conformed to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guideline for Elemental Impurities (ICH-Q3D) based on the 30% control threshold. The content of these impurities varied among the five products (preparations A-E), but in all cases met the oral permitted daily exposure (PDE) criteria stipulated in ICH-Q3D. In 5 lots of preparation C and all lots of preparation D, the equivalent cadmium (Cd) intake for a daily maximum dosage of 2 g was higher than the 30% control threshold of 1.5 µg/day. By cluster analysis, preparations A-E were classified into preparations A + B and C + D + E and/or preparations A + B, C + D and E. The present study showed that all 5 preparations sold in Japan meet the PDE value standard of ICH-Q3D, and that preparations A and B meet the 30% control threshold. It is important that for preparations failing to meet the criteria, further improvements need to be sought, and impurities in magnesium oxide preparations need to be monitored to ensure their safety.

Safety and Toxicity Issues of Therapeutically Used Nanoparticles from the Oral Route.

The emerging science of nanotechnology sparked a research attention in its potential benefits in comparison to the conventional materials used. Oral products prepared via nanoparticles (NPs) have garnered great interest worldwide. They are used commonly to incorporate nutrients and provide antimicrobial activity. Formulation into NPs can offer opportunities for targeted drug delivery, improve drug stability in the harsh environment of the gastrointestinal (GI) tract, increase drug solubility and bioavailability, and provide sustained release in the GI tract. However, some issues like the management of toxicity and safe handling of NPs are still debated and should be well concerned before their application in oral preparations. This article will help the reader to understand safety issues of NPs in oral drug delivery and provides some recommendations to the use of NPs in the drug industry.

GuanXinNing Tablet Attenuates Alzheimer's Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits.

Based on accumulating evidence, Alzheimer's disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aβ), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aβ deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

Sustained-release capsules coated via thermoforming techniques

Capsule coatings have a wide range of applications as they afford protection to active pharmaceutical ingredients. However, few studies have focused on capsule coating owing to the sensitivity of hard gelatin shells to solvents and high temperature. In the present study, we aimed to coat capsules using two thermoforming coating techniques: vacuum forming coating (VFC) and centrifugal forming coating (CFC). Rheological and mechanical properties were investigated to comprehensively elucidate the processes and mechanisms underlying the two coating techniques. The corresponding coating integrity and drug release behavior were characterized and compared. Herein, we observed that a lower temperature was more suitable for the VFC process than the CFC process. The drug release rate decreased with the film thickness increased. Both optimal VFC and CFC capsules revealed a 24 h sustained-release property following Fick's diffusion law. The coating thickness distribution was more homogeneous for the VFC capsule than the CFC capsule. With the advantage solvent-free of functional capsule coatings, thermoforming coating techniques are convenient and efficient solutions for small-scale personalized coating of oral solid preparations.

Diabetes insipidus

Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1,2]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response.Differentiation between the three mentioned entities is difficult [5], especially in patients with Primary polydipsia or partial, mild forms of DI [1,6], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8].In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

SummaryBackgroundDrugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease.MethodsIn this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012–003641–15), and is completed.FindingsBetween July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was –2·29 mL (95% CI –6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group.Interpretation12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods.FundingEfficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

ObjectiveTo assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable...

Assessing the effect of ultra-small phospholipid nanoparticles on biochemical parameters of carbohydrate and fat metabolism in patients with combined hyperlipidemia

Abstract Background and aims Based on the developed technology of preparation of ultra-small size phospholipid (PL) nanoparticles without the use of detergents/surfactants and stabilizers drug preparation, exhibiting hypolipidemic properties has been obtained. Preclinical and clinical studies have shown that phospholipid nanoparticles of 20–30 nm (PLN) have activated reverse cholesterol transport and reduced non-high-density lipoprotein cholesterol levels. The aim of the study was to compare the effect of PLN relative to placebo on the selected parameters of carbohydrate and fat metabolism in patients with combined hyperlipidemia. Methods This Phase III, randomized, double-blind, placebo-controlled, parallel-group study was conducted at 4 centers. The patients (pts) received PLN or placebo (1:1), powder for oral solution preparation (500 mg PL/dose) orally 2 times per day for 12 weeks. Biochemical parameters of carbohydrate and fat metabolism were measured. The data is presented in M (s). Statistical analysis was performed using the Mann-Whitney U-test and the Wilcoxon sign rank test. P-value <0.05 was considered statistically significant. Results A total of 100 pts with combined hyperlipidemia were randomized (age 35–70 years, males 58%). The mean age of patients was 56.4 (10.2) years, body-mass index (BMI) – 30.4 kg/m (2). Mean glucose, triglyceride (TG), fasting insulin (INS) and adiponectin (ADN) serum levels at baseline were 5.58 (0.9) mmol/l, 2.38 (0.6) mmol/l, 13.71 (6.03) mU/ml and 7.07 (2.25) μg/ml, respectively. At Week 12, PLN significantly reduced TG and insulin (p=0.03 and p=0.02, respectively). At the same time, the mean adiponectin level was increased (ns). The drug was well tolerated, and no clinically significant laboratory abnormalities were detected. Conclusions PLN therapy is well tolerated with a favorable effect on the chosen parameters of carbohydrate and fat metabolism in patients with moderate combined hyperlipidemia. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Ministry of industry and trade, Ministry of Healthcare of the Russian Federation

Amorphous solid dispersions of cyclosporine A with improved bioavailability prepared via hot melt extrusion: Formulation, physicochemical characterization, and in vivo evaluation

In this study, the amorphous solid dispersions of cyclosporine A (CsA-ASDs) were prepared by hot melt extrusion (HME) with PVP K12 as carrier to improve the oral bioavailability of CsA. The polymers were screened by solubilization and recrystallization inhibition experiments, then the CsA-ASDs were prepared with optimized technological parameters and characterized on thermodynamics and morphology. The results showed that CsA was dispersed among PVP K12 as amorphous form in CsA-ASDs, and the infrared spectrum testified that there was possible hydrogen bond interaction between CsA and PVP K12. The in vivo pharmacokinetics of CsA formulations in rats were analyzed via LC-MS. The AUC of CsA-ASD tablets increased by 7.3 times compared to CsA bulk powder and 3.1 times in contrast to CsA-PM tablets, respectively. The experiment proved that CsA-ASD tablets significantly improved the dissolution and absorption of the drug. This study had a reference value for the bioavailability improvement of oral CsA preparations.

Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug?

Novel oral iron supplements may be associated with a reduced incidence of adverse drug reactions compared to standard treatments of iron deficiency anaemia. The aim was to establish their value-based price under conditions of uncertainty surrounding their tolerability. A discrete-time Markov model was developed to assess the value-based price of oral iron preparations based on their incremental cost per quality-adjusted life year (QALY) gained from the perspective of the NHS in the UK. Primary and secondary care resource use and health state occupancy probabilities were estimated from routine electronic health records; and unit costs and health state utilities were derived from published sources. Patients were pre-menopausal women with iron deficiency anaemia who were prescribed oral iron supplementation between 2000 and 2014. The model reflecting current use of iron salts yielded a mean total cost to the NHS of £779, and 0.84 QALYs over 12 months. If a new iron preparation were to reduce the risk of adverse drug reactions by 30-40%, then its value-based price, based on a threshold of £20 000 per QALY, would be in the region of £10-£13 per month, or about 7-9 times the average price of basic iron salts. There are no adequate, direct comparisons of new oral iron supplements to ferrous iron salts, and therefore other approaches are needed to assess their value. Our modelling shows that they are potentially cost-effective at prices that are an order of magnitude higher than existing iron salts.

Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections

Fungal infections affect millions of people globally and are often unreceptive to conventional topical or oral preparations because of low drug bioavailability at the infection site, lack of sustained therapeutic effect, and the development of drug resistance. Amphotericin B (AmB) is one of the most potent antifungal agents. It is increasingly important since fungal co-infections associated with COVID-19 are frequently reported. AmB is only administered via injections (IV) and restricted to life-threatening infections due to its nephrotoxicity and administration-related side effects. In this work, we introduce, for the first time, dissolving microneedle patches (DMP) loaded with micronised particles of AmB to achieve localised and long-acting intradermal delivery of AmB for treatment of cutaneous fungal infections. AmB was pulverised with poly (vinyl alcohol) and poly (vinyl pyrrolidone) to form micronised particles-loaded gels, which were then cast into DMP moulds to form the tips. The mean particle size of AmB in AmB DMP tips after pulverisation was 1.67 ± 0.01 μm. This is an easy way to fabricate and load microparticles into DMP, as few steps are required, and no organic solvents are needed. AmB had no covalent chemical interaction with the excipients, but the crystallinity of AmB was reduced in the tips. AmB was completely released from the tips within 4 days in vitro. AmB DMP presented inhibition of Candida albicans (CA) and the killing rate of AmB DMP against CA biofilm inside porcine skin reached 100% within 24 h. AmB DMP were able to pierce excised neonatal porcine skin at an insertion depth of 301.34 ± 46.86 μm. Ex vivo dermatokinetic and drug deposition studies showed that AmB was mainly deposited in the dermis. An in vivo dermatokinetic study revealed that the area under curve (AUC0-inf) values of AmB DMP and IV (Fungizone® bolus injection 1 mg/kg) groups were 8823.0 d∙μg/g and 33.4 d∙μg/g, respectively (264-fold higher). AmB remained at high levels (219.07 ± 102.81 μg/g or more) in the skin until 7 days after the application of AmB DMP. Pharmacokinetic and biodistribution studies showed that AmB concentration in plasma, kidney, liver, and spleen in the AmB DMP group was significantly lower than that in the IV group. Accordingly, this system addressed the systemic side effects of intravenous injection of AmB and localised the drug inside the skin for a week. This work establishes a novel, easy and effective method for long-acting and localised intradermal drug delivery.

Recent Advances in Delivering Strategies of Domperidone: Challenges and Opportunities

Domperidone (DMP), a potent gastroprokinetic and antiemetic drug, exhibits poor aqueous solubility and limited oral bioavailability. Therefore, to develop oral preparations with optimized oral bioavailability, the pharmacokinetic parameters of DMP need to be controlled. The present review aimed to discuss the physicochemical characteristics of DMP causing its unfavorable oral delivery, to explore the viable oral formulation approaches, and to propose some recent formulation approaches that can mitigate the above mentioned difficulties in delivering DMP. In this study, some effective strategies in terms of pharmacokinetic behavior of DMP have been comparatively discussed. It has been recommended that, the amorphous solid dispersion approach could be more convincing from the scalability perspective along with its significant improvement in dissolution behavior and oral bioavailability. Finally, some future perspectives of these strategies have also been addressed to facilitate efficient formulation development.

S221 A Post-Hoc Safety Analysis of Oral Sulfate Tablet Preparation in Elderly Patients and Patients With Renal Insufficiency

Introduction: A new Oral Sulfate Tablet (OST) bowel prep was recently FDA approved, and contains the established osmotic agents sodium and magnesium sulfate, as well as potassium chloride to mitigate diarrheal electrolyte losses. Two pivotal studies in adults were conducted to evaluate OST safety compared to the FDA-approved preps sodium picosulfate and magnesium citrate (P/MC) and PEG3350 plus electrolytes and ascorbate (PEG-EA). A post-hoc analysis compared the pooled OST group to the comparators in the elderly and those with moderate renal insufficiency. Methods: Elderly patients (65-85 yoa) and those with moderate renal insufficiency (GFR 30-60 ml/min/1.73 m2) were included. Patients with severe renal insufficiency or ESRD were excluded from the studies. Patients took the preps in a split-dose (PM/AM) regimen per approved FDA labeling. OST patients consumed 12 tablets and 48 oz of water, per-dose. ECGs and chemistries were collected at baseline, day of colonoscopy, 24-48 hrs post exam, and 7 and 30 days post exam (if required). Adverse events (AEs) were collected via spontaneous reports and solicited collection of typical prep symptoms. Results: 313 patients in the studies were elderly or had moderate renal insufficiency (OST = 161, PEG-EA = 97, P/MC = 55). Average age was 69 years, with 55% being female. Chemistry data confirmed that OST had negligible impact on renal indicators, with fewer than 1% shifting abnormal for creatinine or GFR. This was consistent with the control preps and the non-elderly/renal group. Few elderly/renal subjects (< 5%) experienced an increase in creatinine > 0.3 mg/dL, or GFR decrease > 25%, confirming the preps did not adversely impact renal function. Electrolyte shifts were rare and similar between preps. PEG-EA had fewer Mg shifts due to it’s formula containing no Mg. ECG parameters showed no differences between preps, or when compared to the non-elderly/renal OST group. There was no difference in spontaneously-reported AEs between preps in the elderly/renal group. No OST patients experienced a renal/urinary AE. OST patients reported a higher rate of solicited GI symptoms, however these were generally mild with < 2% rated as severe. There was no difference in frequency between elderly/renal and non-elderly/renal OST patients for any AE. No OST patient in this group experienced a serious AE. Conclusion: This post-hoc analysis confirms that OST is safe for use in the elderly, and patients with moderate renal insufficiency.

Route of Administration of Corticosteroids and Asthma Relapse after Acute Care; Appraisal of Evidence on Effectiveness and Safety

Patients managed for acute exacerbation of asthma in acute settings respond to standard management protocol involving systemic and oral steroids. However, relapses are common due to poor adherence to tapering doses of oral steroids. Intramuscular (IM) administration of corticosteroids has been shown to be equipotent to oral steroids with the added advantage of convenient dosing and improved adherence. However, the role of the route of administration of corticosteroids related to relapse of asthma attacks after acute care has not been fully explored. To find and appraise up-to-date evidence in the literature that compares the effectiveness and safety of IM corticosteroids o a short-course oral corticosteroid in the treatment of asthma patients in acute care settings. The principles of evidence-based medicine (EBM) were used. Suitable articles were identified using MEDLINE, Cochrane library, and Google scholar. Titles and summary texts were reviewed. The full article of the relevant article was downloaded for critical appraisal of methodological quality using a measurement tool to assess systematic review 2 (AMSTAR 2). In applying AMSTAR 2 to the selected systematic review article, it was noted that the investigators followed most of the requirements. However, adequate investigation of publication bias and discussion of its likely impact on the review’s result was not done by the researchers. No significant differences in effectiveness and safety were observed between IM corticosteroids and oral corticosteroids among this category of patients. Additional studies are required to compare different IM and oral corticosteroid preparations. Keywords: Acute exacerbation of Asthma, AMSTER 2, Evidence-based medicine, Route of administration of corticosteroids.

Czy preparaty lewodopy z karbidopą oraz lewodopy z benserazydem są klinicznie równoważne?

Parkinson’s disease is the only neurodegenerative disease that can be effectively treated symptomatically. Treatment of motor symptoms is based primarily on the use of drugs that increase the activity of the nigrostriatal dopaminergic system and compensate for dopamine deficiency. Levodopa remains the gold standard of dopaminergic therapy. It is the most effective and best tolerated anti-parkinsonian drug, it causes the fewest side effects, also in the elderly patients. Oral preparations of levodopa additionally contain one of the aromatic L-amino acid decarboxylase inhibitors: benserazide or carbidopa. Inhibitors have a beneficial effect on the bioavailability of levodopa in the central nervous system, its clinical efficacy and tolerability. In practice, according to common opinion, the preparations of levodopa with carbidopa and levodopa with benserazide are clinically equivalent and can be used interchangeably. The case of a 69-year-old patient treated for 6 years for Parkinson’s disease is presented. The patient presented motor symptoms of advanced Parkinson’s disease: wearing-off motor fluctuations and peak dose dyskinesia. The was treated with levodopa in a dose of 5 × 200 mg (preparation of levodopa with benserazide) as a monotherapy. Due to the worsening availability of the drug used so far in pharmacies, it was changed to a preparation containing levodopa and carbidopa, while maintaining the same dose of levodopa. During the next visit, the patient reported that the change of the formulation had a beneficial effect in the form of a slight but significant reduction in the incidence and severity of peak dose dyskinesia. Pharmacokinetic studies showed that the mean maximum concentration of levodopa after administration of levodopa + benserazide was significantly higher than after administration of levodopa + carbidopa. The preparation containing benserazide caused a rapid increase and then a rapid decrease of the lewodopa plasma concentration. When levodopa was combined with carbidopa, the concentration of levodopa increased and decreased slowly. The results of these pharmacokinetic studies may explain the patient’s observation of the amelioration of peak dose dyskinesia after switching from a levodopa + benserazide formulation to a levodopa + carbidopa combination.

Oral Semaglutide: A Novel Oral Preparation of GLP-1 Receptor Agonist

The glucagon-like peptide-1 (GLP-1) is an endogenous hormone produced by the L cells in the intestine. It is released in response to the intake of food and intestinal dilatation. It stimulates the pancreatic beta-cell to secrete insulin which is dependent upon ingestion of food. GLP-1 acts to slow down gastric motility and suppress appetite through the GLP-1 receptors in the satiety center

Current views on the pharmacological correction of iron deficiency conditions in gynecological practice

The review considers features of iron and folic acid (FA) pharmacokinetics, which affect the effective micronutrient support: molecular mechanisms of absorption and distribution, homeostatic processes of maintaining plasma vitamin and mineral levels by the feedback mechanism, including by regulating the deposition. An important characteristic of ferrokinetics is the presence of unique iron exporter ferroportin which is controlled by a family of iron regulatory proteins. Systemic ferrotherapy and oral rout of iron delivery are distinguished. In general, parenteral iron preparation complexes consist of Fe(III) oxide/hydroxide core stabilized by a carbohydrate polymer shell. Once entering the bloodstream, iron complexes are absorbed by resident macrophages of the reticuloendothelial system of the liver, spleen and bone marrow. Systemic Fe(III) preparations are prodrugs, the active part of which, i.e. iron is released in the lysosomal matrix of phagocytes. Oral iron preparations are divided into those containing bivalent (ferrous) and trivalent (ferric) iron. The article discusses factors determining the differences in the absorption of oral ferrous and ferric iron preparation, the spectrum of side effects, as well as key pharmaceutical approaches to increase the tolerance and adherence of ferrotherapy. These include using preparations containing Fe(II) organic compounds that have a lower dissociation rate than inorganic iron salts as well as slowing down the release of the active Fe(II) pharmaceutical substance from the drug. The review pays special attention to folates as iron synergists and examines the features of FA pharmacokinetics, the molecular basis of synergism, and substantiates the use of combined iron and FA preparations.

A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy.

To evaluate the efficacy, tolerability, and cost of four commonly prescribed oral iron preparations: ferrous sulfate (FS), ferrous fumarate (FF), ferrous ascorbate (FA), and carbonyl iron (CI) in the treatment of iron-deficiency anemia (IDA) in pregnant women. It was a prospective, randomized, open-label, blinded endpoint (PROBE) design with four parallel active control groups: FS, FF, FA, CI. The primary outcome was the proportion of participants becoming non-anemic (Hb ≥ 11 g%) at the end of the study period. The secondary outcomes were the proportion of participants achieving normal red blood corpuscular indices such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration; the proportion of participants achieving normal iron indices such as serum iron, serum ferritin, total iron-binding capacity, and transferrin saturation; and comparison of incidence of any adverse events between treatment groups and comparison of costs of individual drug therapy between treatment groups. One hundred and twenty patients were randomized to four different groups (n=30). The results of the present study show that all the four iron salts at the dose of 200 mg elemental iron per day were equally effective in improving hemoglobin concentration and other hematological parameters. The adverse effects were more common in the FF group (56.7%). The pharmacoeconomic analysis showed that all the drugs are equally cost-effective. To conclude from the results of the present study, it can be said that FS, FF, FA, and CI are equally effective in treating IDA and they can be prescribed interchangeably.