Oral Solution Research Articles

Pharmacokinetics, Efficacy, and Safety of Upadacitinib in Pediatric Patients with Polyarticular-Course Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-label, Phase 1 Trial.

This work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received bodyweight-based upadacitinib doses using a twice-daily (BID) oral solution or once-daily (QD) extended-release tablet based on their body weight and ability to swallow tablets. The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety evaluation for up to 156 weeks, including an additional long-term safety cohort. This interim analysis included available pharmacokinetic and safety data and efficacy data collected through Week 48. A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately 3 hours and 1 hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half-life was approximately 5 hours and 2 hours, respectively. Juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR)30/50/70/90/100 responses at Week 12 were 91.8/89.8/69.4/49.0/32.7%, respectively. Efficacy was generally maintained through Week 48, and improvement in additional efficacy endpoints was also observed. At a median exposure duration of 412 days, 52 of 57 patients reported adverse events, of these 6 experienced serious adverse events. Adverse events were predominately mild to moderate in severity and consistent with the known safety profile of upadacitinib. This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.

Orally Administered Peppermint Oil Solution in Small Bowel Capsule Endoscopy: A Novel Approach to Improve Completion Rates in Patients at Risk of Dela

Background and Study Aims Small bowel capsule endoscopy (SBCE) is crucial in diagnosing small bowel diseases, yet incomplete examinations often result from prolonged gastric transit time. This study aimed to assess the efficacy of orally administered peppermint oil solution as a prokinetic agent to improve SBCE completion rates in patients with delayed gastric transit risk factors. Patients and Methods Conducted as a single-centre, prospective, open-label, non-inferiority trial, the study involved 132 patients identified as at risk for delayed gastric transit. Participants were divided into three groups: a peppermint oil solution group (n=57), a real-time monitoring and intravenous prokinetics group (n=75), and a control group without risk factors (n=193). The primary outcomes included SBCE completion rates, gastric transit time (GTT), small bowel transit time (SBTT), diagnostic yield, and bowel preparation quality. Results Completion rates were high and comparable among groups, with 94.7% in the peppermint group, 90.7% in the real-time monitoring group, and 95.3% in the control group. The peppermint group exhibited a significantly shorter mean GTT of 42.3 minutes compared to 57.0 minutes in the real-time monitoring group (p=0.0423). However, the SBTT was longer in the peppermint group at 246 minutes versus 193 minutes in the real-time monitoring group (p=0.0081), though similar to the control group at 228.3 minutes (p=0.2612). Diagnostic yield and bowel preparation quality were consistent across all groups. Conclusion Oral peppermint oil solution is a safe and effective alternative to traditional prokinetics, enhancing SBCE completion rates while reducing time and resource use in the endoscopy unit.

Retracted: Safety and efficacy of titrated oral misoprostol solution versus vaginal dinoprostone for induction of labor: A single-center randomized control trial.

X. Wang, C. Zhang, Xia Li, H. Qi, Q. Liu, and J. Lei, "Safety and Efficacy of Titrated Oral Misoprostol Solution Versus Vaginal Dinoprostone for Induction of Labor: A Single-Center Randomized Control Trial," International Journal of Gynecology & Obstetrics 154, no. 3 (2021): 436-443. https://doi.org/10.1002/ijgo.13546. The above article, published online on 17 December 2020, in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Professor Michael Geary; the International Federation of Gynecology and Obstetrics; and John Wiley and Sons Ltd. A third party raised concerns regarding errors in the reported data and statistics of the article. An external statistician reviewed the data and was not able to reproduce the listed results for the Bishop score, the post-term pregnancy variable, the gestational hypertension variable, the not using insulin variable, the vaginal delivery variable, and the failed induction variable. In addition, the journal detected numerical errors in Table4, with contradictions between frequencies and reported percentages. The authors did not respond to multiple requests for an explanation and the original data. The editors have determined that the large number of errors identified and lack of original data provided fundamentally compromise the results presented, which necessitates retraction. The authors did not respond to our notice regarding the retraction.

Medicines shortages in the UK: review of the causes and analysis of serious shortage protocols – a mixed methods study

Abstract Introduction Causes of medicines shortages are multifactorial. In February 2019, the Human Medicines Regulations 2012 introduced Serious Shortage Protocols (SSPs) to address medicines shortages. SSPs are issued by the Department of Health and Social Care and enable pharmacists to supply alternative medicines without amended prescriptions1. Aim This review aimed to explore contemporary reasons attributed to medicines shortages in the United Kingdom (UK) and analyse expired SSP records. Methods A rapid scoping literature review was conducted using National Library of Medicine (PubMed®) and Elsevier (ScienceDirect). Grey literatures were collated from the Pharmaceutical Journal, Google, and Public Health England’s grey literature index. Searches were limited to publications written in English, published since 2014, which met the inclusion criteria (medicines OR drugs AND shortages AND causes). Data extraction and analysis was performed using Microsoft Excel. Expired SSPs were extracted to Microsoft Excel and analysed using descriptive and inferential statistics on R software (v.4.3.2). SSP data is publicly available; therefore, no ethical approval was required. Results Causes of Medication Shortages A total of 11 papers were selected, in which 77 medicines shortage causes were discussed. Narrative analysis identified 10 shortage-drivers. The most frequent were Manufacturing and Quality Challenges (30%,23/77), Business and Commercial Issues (21%,16/77), and Regulatory Changes and Challenges (10%,8/77). Content analysis found that supply-driven issues were more frequently cited than demand-driven issues. SSP Analysis Between October 2019 and June 2024, 59 SSPs had expired2. Menopausal Hormonal Treatments (MHTs) were the most common medication class in shortage (41%,24/59), followed by antibiotics (17%,10/59), and antidepressants (12%,7/59). The mean shortage length was 129.2 days (IQR=51–196), the longest lasting 359 days (oestradiol 0.5mg/1mg gel sachets). Oestradiol transdermal medications accounted for 19 of 24 MHT SSPs. The mean MHT shortage length was 152.6 days (IQR=51.0–216.0). Phenoxymethylpenicillin accounted for 8 of 10 antibiotic shortages. All 8 phenoxymethylpenicillin SSPs were active from 15 December 2022 to 12 May 2023; 7 of 8 were oral solution formulations. The mean antibiotic shortage length was 168.8 days, which is significantly longer than the whole sample average (p&amp;lt;0.05, IQR=147.0–148.0). All antidepressant SSPs were fluoxetine capsules. The mean shortage length was 99 days (IQR= 35.5–122.0). Discussion Existing literature suggests supply-driven rather than demand-driven causes of medication shortages are more pertinent; however, most expired SSPs were issued in response to demand-driven factors, such as disease outbreaks and changing prescribing demand. This suggests the extent of demand-driven shortages is not reflected in current literature. Future research should explore how demand-driven causes of shortages can be mitigated. As a rapid scoping review was conducted, the full breadth of literature may not be presented. Additionally, the grey literature findings are limited by potential inaccuracies. Finally, the use of narrative analysis may limit the generalisability of identified shortage drivers. As of 05 June 2024, there are 5 active SSPs. With medicines shortages becoming normalised within the UK health system3, there is an urgent need to mitigate supply- and demand-driven causes. Additionally, further research should explore why certain medication classes are more frequently in shortage than others.

Manipulation of Lipid Nanocapsules as an Efficient Intranasal Platform for Brain Deposition of Clozapine as an Antipsychotic Drug

Background/objectives: The blood–brain barrier (BBB) significantly limits the treatment of central nervous system disorders, such as schizophrenia, by restricting drug delivery to the brain. This study explores the potential of intranasal clozapine-loaded lipid nanocapsules (IN LNCsClo) as a targeted and effective delivery system to the brain. Methods: LNCsClo were prepared using the phase inversion technique and characterized in terms of size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. The pharmacokinetic, safety, and pharmacodynamic effects of LNCsClo were then evaluated in a rat model through intranasal (IN) administration and compared with those of oral and intravenous (IV) Clo solutions. Results: LNCsClo were prepared using a phase inversion technique, resulting in a nanocarrier with a particle size of 28.6 ± 3.6 nm, homogenous dispersion, and high EE% (84.66 ± 5.66%). Pharmacokinetic analysis demonstrated that IN LNCsClo provided enhanced Clo brain bioavailability, rapid CNS targeting, and prolonged drug retention compared to oral and intravenous routes. Notably, the area under the curve (AUC) for brain concentration showed more than two-fold and eight-fold increases with LNCsClo, compared to IV and oral solutions, respectively, indicating improved brain-targeting efficiency. Safety assessments indicated that LNCsClo administration mitigated Clo-associated metabolic side effects, such as hyperglycemia, insulin imbalance, and liver enzyme alterations. Additionally, pharmacodynamic studies showed that LNCsClo significantly improved antipsychotic efficacy and reduced schizophrenia-induced hyperactivity, while preserving motor function. Conclusions: These results highlight the potential of IN LNCsClo as a novel drug delivery system, offering improved therapeutic efficacy, reduced systemic side effects, and better patient compliance in the treatment of schizophrenia and potentially other CNS disorders.

Traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao oral prescription) for the treatment of acute intracerebral haemorrhage: a multicentre, randomised, placebo-controlled, double-blind, clinical trial.

There are few proven treatments for acute spontaneous intracerebral haemorrhage, and they all target reducing expansion of the haematoma. The traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao) in an oral solution is comprised of several Chinese herbs that are widely used to treat patients with intracerebral haemorrhage in China on the understanding that they enhance resorption of the haematoma and reduce neuroinflammation. We aimed to provide a reliable assessment of the safety and efficacy of FYTF-919 in patients with moderate to severe acute intracerebral haemorrhage. We did a pragmatic, multicentre, randomised, double-blind, placebo-controlled trial at 26 hospitals in China. We enrolled adults (age ≥18 years) with a diagnosis of symptomatic spontaneous intracerebral haemorrhage (confirmed by brain imaging) within 48 h after the onset of symptoms (or last seen well), which resulted in moderate to severe neurological impairment defined by scores of at least 8 on the National Institute of Health Stroke Scale or between 7 and 14 inclusive on the Glasgow Coma Scale. Randomisation (1:1) was via a central internet-based system with a block grouping method stratified by provincial location of the hospital, severity of neurological impairment, and site of the haematoma in the brain. FYTF-919 and the placebo were masked through consistency in appearance, smell, taste, and other aspects. Participants were allocated to receive 33 mL (or 25 mL via a nasogastric tube if a participant's swallowing was impaired) of either oral liquid FYTF-919 or matching placebo administered at least 30 min after a meal every 8 h (or 6 h via nasogastric tube) over 24 h for 28 days. The primary efficacy outcome was the utility weighted modified Rankin Scale (a seven-level ordinal scale that ranges from 0 [no symptoms] to 6 [death], in which the utility weights of 0·97, 0·88, 0·74, 0·55, 0·20, -0·19, and 0·00 were assigned to the seven levels respectively, with higher scores indicating a better outcome according to the participants' perspective) at 90 days analysed in a general linear model with adjustment for baseline factors. We did several adjusted and sensitivity analyses. Primary analyses were assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT05066620 and is complete. Between Nov 24, 2021, and Dec 28, 2023, of 9000 patients screened, 1648 were randomly assigned to treatment, 817 to the FYTF-919 group and 831 to the placebo group. Before receiving any treatment two patients in the FYTF-919 group and five patients in the placebo group immediately withdrew their consent leaving 1641 participants with available primary outcome data in the intention-to-treat population, 815 in the FYTF-919 group and 826 in the placebo group. 1242 (75·7%) participants consumed 80% or more of the study medication and 994 (60·6%) consumed all of it within 28 days. Mean utility weighted modified Rankin Scale scores at 90 days were 0·44 in the FYTF-919 group and 0·44 in the placebo group (difference 0·01, 95% CI -0·02 to 0·04; p=0·63). The neutral result was consistent in adjusted and sensitivity analyses. There was no significant difference in serious adverse events. This large, randomised, placebo-controlled, double-blind, clinical trial showed no effect of the traditional Chinese medicine herbal compound FYTF-919 on functional recovery, survival, and health-related quality of life in patients with moderate to severe intracerebral haemorrhage. The results reaffirm the need for methodologically rigorous, randomised controlled trials to evaluate the effectiveness of existing therapies, including traditional Chinese medicines that are already in widespread use throughout the world. Key-Area Research and Development Program of Guangdong Province.

EXCLUSIVE BREASTFEEDING PRACTICE AND ASSOCIATED FACTORS AMONG FIRST-TIME MOTHER IN LARKANA

Exclusive breastfeeding (EBF) is defined as the practice of feedi: Exclusive breastfeeding (EBF) is defined as the practice of feeding infants solely with breast milk for the first six months of life, without introducing any other liquids or solid foods, except oral rehydration solutions, vitamins, or necessary medications. Objective: The main objective of the study is to find the exclusive breastfeeding practice and associated factors among first-time mothers in Larkana, Pakistan. Methods: This cross-sectional study was conducted at Sheikh Zayed Women's Hospital Larkana from June 2023 to December 2023. Data involve 345 breastfeeding first-time mothers as participants. Data were collected through a random sampling technique. Participants were first-time mothers with infants aged between 0-6 months, willing to provide informed consent were included in the study. Mothers with serious health conditions or those whose infants had medical complications preventing breastfeeding were excluded. Results: Data include 345 participants according to the criteria of the study. The majority of participants in the study were aged between 20-30 years (60.3%), with a smaller proportion under 20 years (9.3%) and over 30 years (30.4%). Most had secondary education or less (68%), while 32% had higher education. Regarding employment status, 59.4% were unemployed, and 40.6% were employed. In terms of socioeconomic status, 40% of participants were from low-income groups, 35% from middle-income, and 25% from high-income. In the study, 58% of participants reported practicing exclusive breastfeeding (EBF), while 42% did not. Conclusion: Exclusive breastfeeding rates among first-time mothers remain suboptimal, with significant factors such as maternal age, education, employment status, mode of delivery, and healthcare support playing key roles in influencing EBF practices.ng infants solely with breast milk for the first six months of life, without introducing any other liquids or solid foods, except oral rehydration solutions, vitamins, or necessary medications. Objective: The main objective of the study is to find the exclusive breast-feeding practice and associated factors among first-time mothers in Larkana, Pakistan. Methodology: This cross-sectional study was conducted at Sheikh Zayed Women Hospital Larkana during June 2023 till December 2023. Data involve 345 breast feeding first-time mothers as participants. Data were collected through a random sampling technique. Participants were first-time mothers with infants aged between 0-6 months, willing to provide informed consent were included in the study. Mothers with serious health conditions or those whose infants had medical complications preventing breastfeeding were excluded. Results: Data include 345 participants according to the criteria of the study. The majority of participants in the study were aged between 20-30 years (60.3%), with a smaller proportion under 20 years (9.3%) and over 30 years (30.4%). Most had secondary education or less (68%), while 32% had higher education. Regarding employment status, 59.4% were unemployed, and 40.6% were employed. In terms of socioeconomic status, 40% of participants were from low-income groups, 35% from middle-income, and 25% from high-income. In the study, 58% of participants reported practicing exclusive breastfeeding (EBF), while 42% did not. Conclusion: Exclusive breastfeeding rates among first-time mothers remain suboptimal, with significant factors such as maternal age, education, employment status, mode of delivery, and healthcare support playing key roles in influencing EBF practices.

International Trends in Zinc Treatment for Diarrhea.

Diarrhea is a leading cause of death among children <5 years of age and can have long-term adverse consequences for human development. The World Health Organization has recommended the therapeutic use of zinc for the treatment of diarrhea, along with oral rehydration solutions, since 2004. We studied recent trends in the use of zinc to treat diarrhea in 23 low- and middle-income countries. A repeated cross-sectional design of 46 Demographic and Health Surveys from 23 countries was used to estimate the average annual change in zinc treatment across recent years. The earlier surveys were conducted in different years from 2009 to 2014, and the latest surveys were conducted in different years from 2015 to 2023, with an average gap of 6 years between surveys. A diarrhea episode during the 2 weeks before the survey and the treatment of diarrhea using zinc and oral rehydration solutions among children <5 years old was identified using an interview with mothers. In the pooled sample, the treatment of diarrhea in children <5 years of age using zinc increased from 2% in the earlier surveys to 27% in the more recent surveys, or an average annual increase of 4 percentage points (pp). The prevalence of zinc treatment increased in all 23 countries, ranging from 9 pp per year on average in Sierra Leone to 1 pp in Cambodia. A large increase in the use of therapeutic zinc to treat diarrhea in children was observed in recent years. However, coverage remains incomplete.

Knowledge, Attitude and Practice Regarding Use of ORS in Diarrhoea by Mothers in an Island of Bangladesh

Introduction: The second leading cause of death in under-five children is diarrhea. ORS is a simple and highly effective therapy for managing diarrhea. However inappropriate knowledge of preparation and lack of use of ORS leads to health hazards including increased rate of mortality and morbidity. So aim of this study to assess the knowledge, attitude, and Practice of mothers towards the use of oral rehydration solution in the treatment of acute diarrhea in children. Methods: A cross-sectional study was carried out over eight months (1st May to 30th December 2023) among 510 mothers who had children of six months to five years and had recent episodes of diarrhea. Data were collected by using a semi-structured questionnaire in face-to-face interview. Data were analyzed by using SPSS software program.Results: Among 510 mothers, 47.05% were 20-30 years old, 29.80% were below 20 years and 23.13% were over 30 years. One fourth of them had no institutional education and 36.27% had primary, 20.78% and 18.23% had secondary and tertiary level of education respectively. 40.39% were from lower socioeconomic condition, 31.97% were from middle and 27.64% from upper socioeconomic condition. 100% of family used sanitary latrine though 73.72% use safe drinking water as a preventive part of diarrhea.89.98% of mother was aware about ORS but only 75.88% used ORS in recent episode of diarrhea, among them 63.03% prepared ORS correctly and 60.98% used adequate amount. Age of mothers was not corresponds with the correct preparation and practice of ORS but socioeconomic condition and level of education carried statistically significant value. Conclusion: Knowledge and practice of ORS preparation and used of ORS in recent episode of diarrhea among the mother was unsatisfactory. Improve the Maternal education and socioeconomic status will improve ORS correct preparation and use. Mothers should be taught the importance of optimal use and correct preparation of ORS in diarrhea. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 43-49

Therapeutic mechanism and key active ingredients of Yinxing Mihuan Oral Solution in coronary heart disease comorbidity with anxiety: A network pharmacology and molecular docking approach.

Yinxing Mihuan Oral Solution (YMOS) is a Chinese patent medicine for treating coronary heart disease combined anxiety (CHDCA), but the molecular mechanism of its treatment is still unclear. This article aims to understand the molecular mechanism, optimize clinical drug use, and guide new drug development. Using the Swiss Target Prediction database, we obtained the main chemical composition of YMOS. Then we used network pharmacology to identify their potential targets. Network construction, coupled with protein-protein interaction and enrichment analysis was used to identify representative components and core targets. Finally, molecular docking simulation was conducted to further refine the drug-target interaction. Forty-two active chemicals were found in YMOS and 91 target genes related to CHDCA. The treatment effect was found to be associated with 1908 biological processes and 160 pathways, as revealed by the outcomes of the enrichment analysis. The potential therapeutic mechanisms of the drug are closely related to its antioxidant, anti-inflammatory, and vascular function regulation pathways, and the main core targets include albumin, tumor necrosis factor, TP53, AKT serine/threonine kinase 1, interleukin 1 beta, and vascular endothelial growth factor A. The potential molecular mechanisms of YMOS in CHDCA treatment were identified using network pharmacology and molecular docking approaches. The results reveal the systemic biological implications of YMOS. This study has systematically uncovered the molecular mechanism of YMOS for the first time, offering fresh insights for evidence-based clinical applications.

Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial.

To assess if off-label oral solution of misoprostol compared with licensed oral tablet of misoprostol approved for induction of labour (IOL) is as efficient in resulting in vaginal delivery within 24 h, using a non-inferiority design. Prospective, randomised, non-inferiority, open-label, blinded endpoint trial. Two tertiary level hospitals, Stockholm, Sweden, January 2022 to May 2023. In all, 874 women, without previous caesarean section, with an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks, with a normal cardiotocography, planned for IOL were included. Women were randomised 1:1 to intervention (25 μg oral solution of misoprostol) or control (25 μg oral tablet of misoprostol) two-hourly for a maximum of eight doses. Subsequent methods of induction followed clinical practice. The primary outcome was vaginal delivery within 24 h tested using non-inferiority testing procedures at a non-inferiority margin of 5 percentage points. Secondary efficacy outcomes were tested for superiority of either treatment. Analyses were by intention-to-treat. There were 207 (47.4%) vaginal deliveries within 24 h for women receiving oral solution and 192 (43.9%) vaginal deliveries within 24 h for women receiving oral tablet, establishing non-inferiority with an absolute risk difference of 3.4% (95% CI -3.2% to 10.0%). Women receiving oral solution required fewer doses to reach active labour than women receiving oral tablet (5.7 vs. 6.1, p = 0.007). There were no significant differences for other secondary or safety outcomes. Off-label oral solution of misoprostol was non-inferior to the licensed oral tablet regarding efficacy of IOL defined as vaginal delivery within 24 h. Clinicaltrials.gov identifier: NCT05424445.

Intermittent Preventive Treatment of Malaria in Pregnancy and the Impact on Neonates in African Countries as Assessed by Entropy Weight and TOPSIS Methods.

Background/Objectives: In regions of Africa with a high prevalence of malaria, pregnant women in their first or second trimester should be administered intermittent preventive treatment in pregnancy (IPTp). However, infants may contract malaria despite the IPTp therapy that their mothers have received. The objective of the present investigation was to assess the symptoms and various treatments for neonatal malaria. Methods: Entropy weight and TOPSIS were used to achieve the study goal. The TOPSIS multi-attribute decision-making system was used to assess newborn malaria symptoms and select the optimal treatment, even for mothers receiving IPTp medication during pregnancy. The entropy weight approach calculated TOPSIS attribute weights. The present research used UNICEF data for 14 African nations in 2023. Results: The results indicated that neonates whose mothers received IPTp therapy ultimately contracted malaria, with diarrhea being the primary symptom. It is important to note that health providers administer a combination of zinc and oral rehydration solution (ORS) to infants as the most effective treatment for malaria symptoms, thereby abandoning the first-line treatment for malaria, artemisinin-based combination therapy (ACT). Conclusions: The most effective treatment for neonatal malaria is a combination of zinc and ORS, although less than half of children in Africa have access to ORS. Therefore, the findings of this study may encourage African countries to prioritize co-pack therapy in their procurement and supply, healthcare provider training, and expenditures. This therapy will also help alleviate the symptoms of malaria in neonates.

Cross-sectional study exploring the prevalence and clinical manifestations of acute diarrhea among under-five children in primary care hospital in democratic republic of the congo

Background: Acute diarrhea (AD), which is defined as frequent passing of liquid stools compared to normal, is a serious and worrying problem and remains a concern for health care systems because of its high mortality cause in children under 5 years old. Our study aimed to present the prevalence and to describe the clinical manifestation of AD among under-five children. Methods: From June 2022 to May 2023, we conducted a retrospective, descriptive and cross-sectional study including all patients aged 0 to 5 years hospitalized for AD. Results: Out of 512 patients, only 197 (38.5%) children with AD were selected for our study. The average age is 25.5 months, and the sex ratio is 1.11. Some families (75.1%) have clean latrines, and 21.8% use water from the river. Inaccessibility to clean water and intolerance or food poisoning were the causes of acute diarrhea in children. Major signs and symptoms are fever, dehydration and vomiting. Weight loss and malnutrition are the major complications of AD in children. The treatment of AD is provided by oral rehydration solutions and antibiotics. Conclusion: The study highlights the significant prevalence of acute diarrhea among under-five children underscores the importance of preventive measures and government intervention, such as the introduction of rotavirus vaccination. However, conclusions regarding prevalence rates should be interpreted with caution due to the lack of detailed population data.

Oral rehydration in diarrhea: from history to current guidelines. A review

Acute gastroenteritis (AGE) is usually defined as a change in stool consistency (liquid or unformed) and/or an increase in the frequency of bowel movements, which can also be accompanied by vomiting and fever. Fever increases the metabolic rate by more than 1.5 times; for every 1°C increase in body temperature, fluid loss increases by 10%. AGE is a common cause of morbidity and mortality among infants and children. The prognosis is favorable if the condition is recognized promptly and appropriate treatment is started. The main goal of AGE therapy is to restore water balance and prevent dehydration, which can be achieved with an oral rehydration solution. The composition and proportion of the components of rehydration agents are described in the guidelines of the European Society for Paediatric Gastroenterology Hepatology and Nutrition, of which the Russian Society of Pediatric Gastroenterologists is a collective member, and such agents are fully consistent with the balanced formulations of RehydroStandard and Rehydron Bio rehydration agents. The latter includes the probiotic strain Lactobacillus rhamnosus GG, well studied and recommended by the European Society for Paediatric Gastroenterology Hepatology and Nutrition for acute intestinal infections since this strain reduces the duration and severity of diarrhea according to the results of studies. Rehydron Bio and RehydroStandard can be recommended for use in clinical pediatric practice.

In Vivo Effects of a GHR Synthesis Inhibitor during Prolonged Treatment in Dogs

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile.

EAR CANKER IN A RABBIT – A CASE REPORT

A three-month-old female New Zealand White Rabbit, weighing about 1.4 kg was brought to the Veterinary Clinical Complex, Veterinary College and Research Institute, Tirunelveli with ahistory of intense pruritis and alopecia all over the body. Clinical observation revealed crusty lesions on the nose,ear margin and toes. Microscopic examination of the deep skin scraping revealed the presence of Psoroptes cuniculi mite. The rabbit was treated with an injection Ivermectin @ 0.4 mg/kg sub-cutaneous and an injection of Chlorpheniramine maleate @ 0.4 mg/kg intramuscular and further advised the owner to give HITEK® oral solution (Ivermectin) @ 0.4 mg/kg PO once a week and Benzyl benzoate I.P. solution topically daily for a continuous period of one month along with multivitamin supplementation (Multistar pet®) @ 2 ml PO BID. The rabbit recovered successfully without any drug side effects (Tandem usage of ivermectin and Benzyl Benzoate).

6986 Efficacy and Safety of Weekly Liquid Alendronate Sodium Trihydrate in Korean Postmenopausal Women with Osteoporosis: A 12-Month, Multi-Center, Randomized Trial

Abstract Disclosure: Y. Rhee: None. S. Ahn: None. N. Hong: None. D. Seo: None. S. Hong: None. Background: Although alendronate is the most prescribed oral bisphosphonate for osteoporosis treatment, it can lead to gastrointestinal problems, impacting treatment compliance and efficacy. This study aimed to assess the efficacy and safety of once-weekly alendronate sodium trihydrate (ALN-S), an oral solution, compared to once-weekly alendronate sodium (ALN-T), an oral tablet, in Korean postmenopausal women with osteoporosis. Methods: Conducted as a 12-month, multi-center, prospective, randomized, open-labeled, parallel trial at two hospitals in Korea, 170 postmenopausal women were randomized to ALN-S (N=85) or ALN-T (N=85). Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) was measured at baseline and after 12 months. Bone turnover markers, including C-telopeptide (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), were assessed at baseline, 6 months, and 12 months. The primary outcome was the percentage change in LS BMD, evaluated for non-inferiority. Results: After 12 months, both ALN-S and ALN-T groups exhibited a significant increase in LS, FN, and TH BMD, with no significant intergroup differences (ALN-S: LS 5.0 ± 0.6%, FN 1.8 ± 0.6%, TH 2.2 ± 0.5%; ALN-T: LS 5.2 ± 0.6%, FN 1.6 ± 0.6%, TH 1.8 ± 0.5%). ALN-S was found to be non-inferior to ALN-T for BMD change at LS (treatment difference: -0.22%, 95% CI: -1.84 to 1.40%), excluding the predefined non-inferiority margin of -2.29%. Changes in both CTX and P1NP over time did not significantly differ between the groups. There was no significant difference in the frequency of adverse events between the groups. Conclusion: Weekly liquid alendronate sodium trihydrate demonstrated non-inferiority to weekly tablet alendronate sodium in increasing LS BMD in Korean postmenopausal women with osteoporosis. Presentation: 6/2/2024

Evaluation of the effect of carvedilol orodispersible tablets on ischemia-reperfusion injury and flap viability in rats: An in vivo study.

Flap surgery is an integral part of plastic surgery, and ischemia-reperfusion (I/R) injury significantly affects the viability of the flap. Carvedilol (CRV), a nonselective beta-blocker with alpha-1 blocking and antioxidant properties, and known for its potential in reducing I/R damage, was chosen as the active substance for our study. The aim of this study was to investigate the vasodilator and antioxidant effects of CRV on rat inferior epigastric artery skin flap using orally disintegrating tablets (ODTs). The optimized ODT formulation was subjected to in vivo experiments using Sprague-Dawley female rats (n = 24) divided into three groups: Group I (control, I/R), Group II (treatment, I/R + CRV), and Group III (treatment, I/R), I/R + CRV ODT). Reperfusion was then observed following the release of the microclamp from the pedicle, and the flap was then re-adapted to its original position. Control rats were given oral isotonic solution via gavage and were subjected to 8 h of ischemia and 12 h of reperfusion. Group II was given 2 mg/kg CRV oral tablets for 7 days before and after surgery. Group III was given 2 mg/kg/day CRV ODT for the same period. Biopsies were taken from the flap and histopathological and biochemical analyses including superoxide dismutase, glutathionenitric oxide, malondialdehyde, paraoxonase 1, total oxidant, and total antioxidant capacities were performed. This study demonstrates that CRV ODTs significantly increased flap viability by approximately 25% compared to the control group, highlighting their promising therapeutic potential.

Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC. Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.

Pharmacokinetic Study of Fingolimod Nasal Films Administered via Nose-to-Brain Route in C57BL/6J Mice as Potential Treatment for Multiple Sclerosis.

Fingolimod hydrochloride (FH) has emerged as a vital medication for managing Multiple Sclerosis (MS). Despite its high oral bioavailability of 93%, it is plagued by slow oral absorption (Tmax = 8-12h) and extensive hepatic metabolism. Intranasal administration has emerged as an alternative to address these limitations, ensuring efficient central nervous system delivery and minimizing peripheral exposure and first-pass metabolism. This study aims to develop and evaluate FH nasal films for enhanced drug delivery. A Design of Experiments approach was employed to formulate FH nasal films, utilizing HPMC E50 as a film-forming polymer, PEG 400 as a plasticizer, and Me-β-CD as a permeation enhancer. Two formulations with superior in vitro and ex vivo performance were selected for in vivo evaluation. A comparative pharmacokinetic study was conducted in C57BL/6J mice in the brain and serum after administration of nasal films and oral FH solution, respectively. Sparse sampling and non-compartmental analysis were used. FH nasal films efficiently delivered the drug to both serum (Cmax(F3) = 0.35 ± 0.021, Cmax(F4) = 0.38 ± 0.029μg/mL) and brain (Cmax(F3) = 0.39 ± 0.05, Cmax(F4) = 0.44 ± 0.048μg/mL), achieving higher levels than oral delivery. Brain relative bioavailability (% Frel (0-6 h)) was 519% and 534%, while serum % Frel (0-6 h) was 295% and 343%. The rapid nose-to-brain delivery within 30min, in contrast to 10-h Tmax of the oral solution, indicates the potential of a combined IN and oral treatment regimen. This approach could expedite the attainment of steady-state concentrations, offering a promising method for managing multiple sclerosis (MS).