Intravenous Formulation Research Articles

Intravenous medication errors in the emergency department, knowledge, tendency to make errors and affecting factors: An observational study

BackgroundIntravenous medication errors are common in hospital settings particularly emergency department. This study aimed to determine intravenous medication preparation and administration errors, contributing factors, tendency towards making errors and knowledge level of emergency department healthcare workers. MethodsA cross-sectional study using a structured, direct observation method was conducted. It was conducted with 23 emergency healthcare workers working in the emergency department of a university hospital in Turkey. Data were collected by questionnaires: Knowledge Test on Intravenous Medication Administration, Intravenous Drug Administration Standard Observation Form, Drug and Transfusion Administration Sub-Dimension scale, Perceived Stress Scale and Pittsburgh Sleep Quality Index. ResultsIt was determined that the knowledge level of the emergency healthcare workers about intravenous medication administration was moderate, and the tendency mistakes regarding drug and transfusion applications was very low. There was no relationship between education level, years of work, years of work in the emergency department, perceived stress level and sleep quality, and the tendency of making mistakes in drug and transfusion applications. ConclusionIt is important for patient safety to prevent medication errors by determining the factors affecting intravenous medication administration, tendency to make mistakes and knowledge levels, which are frequently used in emergency department.

A Review on Formulation and Evaluation of Nanoniosomal Topical gel of Paclitaxel for skin cancer

Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the goal for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments. Paclitaxel (PCT) is a chemotherapeutic agent used as a first-line treatment for a wide range of cancers, such as lung, ovarian, breast, prostate, head, and neck cancers, and AIDS-related Kaposi sarcoma. Currently, the marketed forms of Paclitaxel are intravenous formulations. Oral administration of Paclitaxel is unfortunately hampered due to its low bioavailability. This is explained by its low aqueous solubility, low permeability, high affinity for cytochrome P450 and P-glycoprotein. As another approach, drug carrier systems are extensively studied to enhance oral Paclitaxel bioavailability and reduce side effects. The niosomes provides several important advantages over conventional drug therapy. Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer. However, the bilayer in the case of niosomes is made up of non-ionic surface-active agents rather than phospholipids as seen in case of liposomes. Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). The aim of this review is to evaluate the extent of nanotherapeutics used in anti-cancer activity.

Isavuconazole for COVID-19-Associated Invasive Mold Infections.

Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug–drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting.

Preparation and In-vitro Evaluation of Darifenacin HBr as Nanoparticles Prepared as Nanosuspension

Nanosuspension is a term that can be used to describe a colloidal dispersion of nanosized droplets of the drug in an aqueous medium with a size below 1 μm. Drug nanoparticles are one of the most significant methods to reduce the constituent part diameter and increase surface area, improving the dissolution and oral bioavailability of hydrophobic medicines, enhancing drug dissolution rate and bioavailability. Nanoparticles are produced using appropriate techniques for drug delivery applications and administered via various routes, including oral, topical, parenteral, ophthalmic, and pulmonary. Overactive bladder (OAB) affects around 16% of adults and is more common as people become older. It causes a variety of symptoms, including urgency, incontinence, urine frequency, and nocturia. DH. It is newly drug used to treat complicated OAB. It has a higher selectivity for the bladder’s muscarinic receptors. After intravenous and immediate-release oral dose forms. It suffers from extensive first-pass metabolism with a short elimination half-life and ranging between three to four hours). The current research focused on creating an extended-release dosage form utilizing Eudragit RS100. The solvent/anti-solvent precipitation method was used to make darifenacine nanoparticles. A certain quantity of medication was dissolved in a water-miscible solvent (methanol), then poured at a specific speed into water containing stabilizer on a magnetic stirrer for a 1/2-hour; after that, the resulted product was sonicated at 37°C for 15 minutes. The physicochemical interaction among medication with additives was explored utilizing fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC). The particle size and zeta potential of the generated nanosuspension were calculated.

Ketamine and Other Glutamate Receptor Modulating Agents for Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials.

Objective: Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. Method : The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Results: Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. Conclusion: The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.

The Safety, Toleration, and Pharmacokinetics of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers After Increasing Dose Administrations.

Sulfobutyl ether-beta-cyclodextrin sodium salt contained in the marketed intravenous voriconazole injection as a solubilizer may cause harmful accumulations. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of two intravenous voriconazole formulations containing excipients from different manufacturers using increasing dose administrations in healthy Chinese volunteers. A randomized, double-blind, placebo-controlled trial was conducted in three cohorts with 42 healthy Chinese volunteers. Each cohort of 14 volunteers was allocated in proportion (8:4:2) to test the formulation, reference voriconazole, or placebo successively by single-dose then multiple-dose administrations of 3, 4, and 6mg/kg. Forty-one volunteers completed all drug administrations. The pharmacokinetics of test formulations are characterized by high interindividual variability (coefficient of variance of Cmax up to 68.0%, AUC0-τ up to 70.2%, and nonlinear PKs with a regression coefficient of Cmax =1.31 and AUC0-τ =1.75 in a single dose). In the steady state, RAuc of the test drug versus reference drug of the 3, 4, and 6mg/kg dose group were 5.2 and 5.3, 5.6 and 6.3, and 5.8 and 5.5, respectively, and Rcmax were 2.5 and 2.7, 2.6 and 3.1, and 2.8 and 2.6, respectively. Eighty-three adverse events with 37 transient visual disturbances were mild. PKs with high interindividual variability, nonlinear characteristics, and significant dose-dependent accumulation were comparable between the two formulations. Overall, the safety of the test formulation was acceptable.

A profile of delafloxacin in the treatment of adults with community-acquired bacterial pneumonia

Introduction Community-acquired bacterial pneumonia (CABP) is the most common infectious cause of hospital admission in adults, and poses a significant clinical and economic burden. At the same time, antimicrobial resistance is increasing worldwide with only a few new antibiotics developed in recent years. Delafloxacin is an anionic fluoroquinolone available in intravenous and oral formulations and with a broad spectrum of activity targeting Gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA), gram-negative organisms, and atypical and anaerobic organisms. It also has a better adverse event profile compared to other fluoroquinolones. Areas covered This article reviews the current epidemiology of CABP, etiologic agents and current resistance rates, current treatment guidelines, characteristics of delafloxacin (chemistry, microbiology, PK/PD), clinical efficacy and safety in pneumonia and other indications, and regulatory affairs. Expert opinion : Delafloxacin’s susceptibility profile against respiratory pathogens, bioequivalent intravenous and oral formulations and favorable safety profile, support its use for the treatment of CABP. It could be useful as empirical treatment in countries with high rates of penicillin-resistant S. pneumoniae and in patients with suspected or documented pneumonia due to MRSA. In post-influenza staphylococcal bacterial pneumonia, MRSA could be also considered an important pathogen.

RJX Improves Wound Healing in Diabetic Rats.

BackgroundWe recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). The primary objective of the present study was to examine the effects of GMP-grade RJX on wound and burn injury healing in diabetic rats.MethodsIn the present study, a rat model of T2DM was used that employs HFD in combination with a single injection of STZ intraperitoneally (i.p) at a moderate dose level (45 mg/kg). Anesthetized diabetic rats underwent full-thickness skin excision on the back or were subjected to burn injury via a heated brass probe and then started on treatments with normal saline (NS = vehicle) or RJX administered via intraperitoneal injections for three weeks.FindingsNotably, diabetic rats treated with the 1.25 mL/kg or 2.5 mL/kg RJX (DM+RJX groups) rapidly healed their wounds as fast as non-diabetic control rats. Inflammatory cell infiltration in the dermis along with fibrin and cell debris on the epithelial layer persisted for up to 14 days in the DM+NS group but not in RJX-treated groups. The histopathological score of wound healing on days 7 and 14 was better in diabetic rats treated with RJX than diabetic rats treated with NS and comparable to the scores for non-diabetic healthy rats consistent with an accelerated healing process. The residual wound area of RJX-treated rats was significantly smaller than that of NS-treated diabetic rats at each evaluation time point (P<0.001). The accelerating effect of RJX on diabetic wound healing was dose-dependent. We obtained similar results in the burn injury model. Our results demonstrate that RJX – at a dose level >10-fold lower than its clinical maximum tolerated dose (MTD) – accelerates the healing of excision wounds as well burn injury in diabetic rats.

Use of intravenous valproate in acute manic: about a clinical case

IntroductionAcute mania can have behavioral effects such as agitation, being a frequent cause of presentation in the emergency department. Pharmacological treatments include mood stabilizers and atypical antipsychotics. Valproate is an effective drug. However, the intravenous formulation is relegated to other pathologies, such as epilepsy.ObjectivesThe objective was to review the use of intravenous valproate in acute mania in the literature and present its use through a clinical case.MethodsA clinical case using intravenous valproate to treat an episode of acute mania is described and the scientific literature of the last 5 years is reviewed.Results A 43-year-old patient attended the emergency department with a diagnosis of bipolar disorder type I in manic episode with agitation, rejection of oral medication, brought in by the police due to risk of aggression against family members, who reported that the patient had stopped taking her usual medication with valproate 500 mg / 24h and quetiapine 200 mg / 24h threemonths ago. Due to the possibility of having intravenous valproate, it was decided to administer 300 mg intravenously, as well as haloperidol 5 mg intravenously, and hospitalization was decided. The patient had a favorable evolution, with no side effects to the medication, and oral treatment was started after 8 hours, with a good response. In the literature there are few studies in this regard, although the most of them approved the use of valproate as a loading dose in acute mania.ConclusionsIntravenous valproate is an effective, safe, and tolerated treatment in acute mania. More studies are needed to collect precise information.DisclosureNo significant relationships.

Subcutaneously-Administered Infliximab in the Management of Rheumatoid Arthritis: A Short Narrative Review of Current Clinical Evidence.

The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data.

Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration.

BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and Clinical ImportanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.

Comparison of Ketorolac and Indomethacin for the Closure of Patent Ductus Arteriosus among Preterm Infants Born at the Philippine General Hospital: A Randomized Controlled Crossover Design

Background. Indomethacin has been the gold standard for the closure of patent ductus arteriosus (PDA). Still, the availability of the intravenous (IV) form has been a big issue precluding its use in the Philippines. IV ketorolac is another non-steroidal anti-inflammatory drug (NSAID) that is cheaper and more available in our country and used for post-cardiac surgery pain management among neonates.&#x0D; Objectives. To compare the efficacy of ketorolac versus indomethacin in the closure of patent ductus arteriosus among preterm infants.&#x0D; Methods. We conducted a randomized controlled, double-blind, crossover design, non-inferiority trial on the use of iindomethacin versus ketorolac among preterm infants with PDA. We enrolled preterm infants at 5-12 days postnatal life, diagnosed with PDA by echocardiography at the Philippine General Hospital (PGH). We excluded infants with upper gastrointestinal bleeding, renal failure, birthweight &lt; 500 grams, septic shock, and lethal anomalies. Patients were randomly allocated between two treatment groups (indomethacin versus ketorolac). The primary outcome measure was PDA closure measured after the treatment course. Adverse events like oliguria and bleeding were recorded.&#x0D; Results. A total of 27 preterm infants were randomly assigned to the indomethacin (0.2 mg/kg/dose) and ketorolac (0.6 mg/kg/dose) group. Ketorolac has a 60% success rate for PDA closure (9/15) compared to indomethacin 41.67% (5/12) (p=0.154). No renal insufficiency and bleeding diathesis were noted. Five patients died in the study, four in the group initially allocated in ketorolac and one in indomethacin. Causes of death were late-onset sepsis, bronchopulmonary dysplasia, and congenital adrenal hyperplasia.&#x0D; Conclusion. The success rate of PDA closure between IV ketorolac and IV indomethacin was not significantly different. There was neither oliguria nor bleeding observed in both groups.

Ganaxolone: First Approval.

Ganaxolone (ZTALMY®; Marinus Pharmaceuticals) is a synthetic neuroactive steroid that acts as a positive allosteric modulator of the gamma-aminobutyric acid (GABA)A receptor complex. Ganaxolone received its first approval in March 2022 in the USA for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2years of age and older. Approval was based on the results of a multinational phase III trial, in which ganaxolone was effective in reducing seizure frequency in children and adolescents with CDD. In the EU, a Marketing Authorization Application has been filed for ganaxolone in the treatment of seizures associated with CDD and an opinion from the Committee for Medicinal Products for Human Use is expected later this year. Oral ganaxolone is also currently undergoing phase III evaluation in the treatment of tuberous sclerosis complex-related epilepsy, while an intravenous formulation of ganaxolone is being evaluated in refractory status epilepticus. This article summarizes the milestones in the development of ganaxolone leading to this first approval for seizures associated with CDD.

Survey of iron prescribing practices for post-partum anaemia.

Treatment for postpartum anaemia frequently entails iron supplementation, but questions remain regarding its optimal dosing, frequency, and efficacy. Our objective was to learn about the current prescribing practices of obstetrical providers at multiple hospitals, including indications and regimens used; further, we sought to understand how these practices are learned. A 10-question web-based survey was developed via expert consensus. The survey was distributed via email to obstetrical providers (including trainees) practising at seven hospitals affiliated with the University of Toronto, including from Obstetrics & Gynaecology (OBGYN), Family Practice (FP-OB) and midwifery. The survey was directly sent to 469 participants and 140 responses were collected from the direct email recruitment pool (response rate 30%). Half of respondents were OBGYN physicians. The most common indication was a post-partum haemoglobin threshold of 90 g/L. Both intravenous and oral formulations were used; the most common oral formulation was ferrous fumarate (77%). Prescribing practices were most commonly shaped using passed-down knowledge. Through this survey, we have learned about the most common post-partum iron supplementation indications, formulations and regimens used in both academic and community hospitals in the greater Toronto area. This insight will help inform future studies investigating the efficacy of oral iron supplementation in the treatment of post-partum anaemia.

Efficacy of lacosamide in the treatment of non-convulsive seizure and non-convulsive status epilepticus in septic patients: a narrative review

Non-convulsive seizures (NCS) and non-convulsive status epilepticus (NCSE) are of the acute complications of patients admitted to the intensive care unit (ICU), which lead to increased mortality and morbidity. In these cases, immediate treatment with antiepileptic drugs (AEDs) is important to prevent further damage to the brain. AEDs are the first line of treatment, however, most of these medications have many side effects. In the recent years, significant advances have been made in this area and lacosamide is one of the therapeutic options. The intravenous formulation of this drug is most popular due to the lack of drug-drug interaction and properly designed studies which have been conducted in this field. In this review, the latest findings on the effect of lacosamide on acute non-convulsive and generalized-convulsive seizures (G-CS) are evaluated in critically ill patients admitted to the ICU.

Intravenous iron for the treatment of iron deficiency anemia in China: a patient-level simulation model and cost-utility analysis comparing ferric derisomaltose with iron sucrose

Objectives Two intravenous (IV) iron formulations, ferric derisomaltose (FDI) and iron sucrose (IS), are currently available for the treatment of iron deficiency anemia (IDA) in China. Clinical studies have demonstrated that FDI has an improved efficacy and safety profile versus IS, while requiring fewer infusions to correct iron deficits. Based on these findings, the present study evaluated the costs and benefits of FDI and IS for the treatment of IDA, from a healthcare system and societal perspective in China. Methods A patient-level model was developed to project time to hematological response and incidence of cardiovascular adverse events and hypersensitivity reactions (HSRs) associated with FDI and IS over 5 years. Costs included iron acquisition, administration, and adverse event/HSR treatment costs, based on published studies, fee schedules, and a physician survey. Health state utilities associated with adverse events, HSRs, and the number of infusions were obtained from the literature and a time trade-off survey. Results From a healthcare system perspective, FDI was associated with incremental costs of RMB 1,934 (purchasing power parity USD 462) and incremental quality-adjusted life expectancy of 0.078 quality-adjusted life-years (QALYs) versus IS, yielding an incremental cost-utility ratio of RMB 24,901 (USD 5,949) in the base case scenario. From a societal perspective, FDI was associated with reduced total costs and therefore dominant versus IS. Limitations Limitations included the absence of clinical data specific to China and insufficient data to model persistence with treatment. Conclusions This was the first cost-utility analysis comparing FDI and IS for the treatment of IDA in China. Based on a patient-level model, FDI was found to improve quality of life and reduce administration and adverse events costs relative to IS. Using the 2020 Chinese gross domestic product per capita of RMB 72,447 (USD 17,307) as a cost-effectiveness threshold, FDI would be considered cost-effective in China.

Effects of ferric carboxymaltose on phosphate and calcium homeostasis in a murine model of iron‐deficiency anemia

Iron deficiency anemia (IDA) can be caused by heavy uterine bleeding, inflammatory bowel disease, or chronic kidney disease. Ferric carboxymaltose (FCM) is an intravenous form of iron replacement therapy that has been shown clinically to induce severe hypophosphatemia. However, the mechanism by which this occurs is poorly understood. The objective of this study was to develop and characterize a mouse model that would allow investigating the effects of FCM on phosphate (Pi) and calcium (Ca2+) homeostasis. Female C57Bl/6J mice (n=40; 10/group) were randomized to either iron deficient (ID) diet (4 ppm iron) or control diet (48 ppm iron) for 4 weeks followed by intravenous bleeding (0.7% of body weight) 4 and 2 days prior to starting the study. Baseline blood and urine was collected for hematocrit, complete blood count, and serum and urine Pi and Ca2+ levels. Subsequently, mice were treated with a single IV injection of either vehicle (saline) or FCM (20 mg/kg) via retroorbital injection. One week later, terminal blood, urine, feces, liver, and spleen were collected. At baseline, compared with controls, ID mice had lower hematocrit (35±1% vs 39±1%; P&lt;0.05) and microcytic hypochromic anemia. After 7 days, FCM‐treated ID mice had significantly higher hematocrit compared with vehicle‐treated ID mice (43±1% vs 30±1%; P&lt;0.05). FCM treatment also significantly increased iron content in liver and spleen in control mice (18±1 vs 6±1 μmol/g and 36±2 vs 27±3 μmol/g, respectively; P&lt;0.05) and ID mice (16±1 vs 1±0.1 μmol/g and 21±2 vs 6±1 μmol/g, respectively; P&lt;0.05). At baseline, urinary Pi/creatinine ratios were significantly lower in ID mice compared with controls (30±5 vs 58±7 mmol/mmol; P&lt;0.05); however, FCM treatment in ID mice did not affect urinary Pi/creatinine ratios after 7 days (31±6 vs 18±5 mmol/mmol; not significant). There were no differences between groups for serum Pi, erythrocyte Pi, or fecal Pi. Under baseline conditions, no differences in plasma Ca2+ or urinary Ca2+/creatinine ratios were observed between groups; however, FCM‐treated ID mice had significantly lower plasma Ca2+ levels after 7 days compared with ID mice at baseline (2.3±0.1 vs 2.6±0.1 mmol; P&lt;0.05) and lower urinary Ca2+/creatinine ratios (0.1±0.1 vs 1.3±0.2 mmol/mmol; P&lt;0.05). We speculate this may be due to increased PTH and FGF23 levels in FCM‐treated ID mice. In summary, our study demonstrates for the first time that FCM affects Pi and Ca2+ homeostasis in a murine model of IDA. Further studies are needed to better understand the mechanisms of FCM on mineral homeostasis as well as the driving factors for species differences.

Real-World Evidence of Efficacy and Safety of Levonadifloxacin (Oral and IV) in the Management of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Findings of a Retrospective, Multi-Center Study.

BackgroundAntimicrobial resistance by bacteria poses a substantial threat to the success in the treatment of acute bacterial skin and skin structure infections (ABSSSI). Levonadifloxacin is a novel benzoquinolizine subclass of quinolone which has a broad spectrum of activity, available in both oral and intravenous formulations for the treatment of skin structure infections caused by Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA).Patients and methodsThis prescription event monitoring study captured data of 227 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of ABSSSI. Study outcomes were a clinical and microbial success at the end of therapy and safety was assessed based on adverse events reported.ResultsOne hundred and forty patients received IV levonadifloxacin therapy, 76 patients received oral alalevonadifloxacin, and 11 received IV followed by oral therapy. The mean duration of therapy was 7.3 days. Out of 227 patients, MRSA isolates were identified in 79 patients. Clinical success rates with oral, IV, and IV followed by oral levonadifloxacin therapy were 97.3%, 97.8%, and 100% respectively. The overall microbial success rate was 99.2% and only two patients reported two adverse events.ConclusionsThe excellent safety and efficacy profile of levonadifloxacin on oral and/or intravenous therapy, makes it a desirable treatment modality for management of ABSSSI. Unique features of levonadifloxacin such as availability of both IV and oral form, minimal drug-drug interactions, exemption from dosage adjustment in renal and hepatic impaired patients and a broad spectrum of coverage, makes it a suitable agent meeting several unmet clinical needs in contemporary patients.

A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan.

Background:Anaemia affectsmore than half ofAfrica'spregnancies.Standard care, with oral iron tablets,often fails to achieve results, with complianceandgastrointestinalside-effectsbeing a significant issue.In recent years,intravenousiron formulations havebecomesafe,effective,and quick to administer, allowingthecompleteiron requirementsofpregnancyto beprovidedin one15-minuteinfusion.The Randomized controlled trial of the Effect ofintraVenousiron on Anaemia in Malawian Pregnant women (REVAMP)will evaluate whethera modern intravenous ironformulation,ferriccarboxymaltose(FCM),given once during the second trimesteriseffective and safein improving maternal and neonatal outcomes for treatment of moderate to severe anaemiainsub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods:REVAMP is amulticentre, two-arm,open-label,parallel-grouprandomizedcontroltrial(RCT)in 862 pregnantwomen in their second trimester.The trial statistician developed the statistical analysis planin consultation with thetrial managementteambased on the protocol, data collection forms, and study outcomes available in the blinded study database. Results:The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions:A statistical analysis planallows for transparency as well as reproducibility of reporting and statistical analyses.

Intravenous posaconazole: key features of clinical pharmacology and practical applications

Invasive fungal infections in various categories of patients remain one of the most urgent problems of modern medicine. This is complicated by the imperfection of diagnostic methods, as well as a small range of antimycotics for systemic use. The market launch in 2005 of posaconazole, a second-generation systemic antimycotic from the group of triazoles with a wide spectrum of activity in the form of an oral suspension, was an event in medical mycology. However, pharmacokinetic features of suspension have caused certain problems with its use. The suspension was replaced by a tablet form, largely devoid of these shortcomings, and then a solution for intravenous administration, which was registered in Russia at the end of 2021 (significantly later than in other countries of the world). Registration of an intravenous form of the drug with the possibility of using both for a stepdown approach and in patients who, for different reasons, cannot take posaconazole orally, had a positive impact on the problem of choosing antimycotics for the prophylaxis and treatment of invasive fungal infections. In this article, we will consider the features of the clinical pharmacology of the intravenous form and its place in the prophylaxis and treatment of invasive mycoses.