Tablet Dosage Research Articles

Desmopressin dosing in children using real-world data and pharmacokinetic/pharmacodynamic model simulations.

Variability in pediatric dosing of desmopressin (ddAVP) in AVP-deficiency (AVP-D) is well-documented but dosing recommendations are limited. This study evaluates and optimizes ddAVP dosing regimens in children with AVP-D using pharmacokinetic and pharmacodynamic (PK/PD) simulations. Retrospective electronic health record review was done to identify children (<18 years) with AVP-D on ddAVP evaluated in the outpatient setting using ICD 9 and 10 codes. A previously developed PK/PD model from Michelet et al was used to simulate ddAVP concentrations and urine rates based on a child's age and ddAVP dose. The effects of demographic characteristics (age, weight, etc.) on dose and urine rate were investigated through simulations to optimize doses of ddAVP for children who were wet overnight. A total of 276 dosing records were identified among 53 children with AVP-D. Simulations indicated that in children under 5 years of age who were wet overnight, increasing the outpatient dose to 50 mcg was predicted to decrease urine rate to a pattern similar to those who remained dry. An initial outpatient dose of at least 50 mcg for children between 1 and 5 years of age would improve efficacy of ddAVP. 50 mcg is likely a safe initial outpatient dose of oral desmopressin tablet for young children 1-5 yrs of age with central Diabetes Insipidus/AVP-Deficiency. We confirmed that desmopressin doses vary greatly in children with central Diabetes Insipidus/AVP-deficiency. Real-world clinical data can be leveraged to improve medication dosing in rare diseases.

Impact of Banhabaekchulcheonmatang (Banxia Baizhu Tianma Tang) and Hwangryeonhaedoktang (Huang Lian Jie Du Tang) on Edoxaban: Herb-Drug Interaction Study in Healthy Subjects

Concurrent use of traditional herbal medicines and conventional drugs, particularly for stroke treatment, is widespread, raising concerns about potential drug interactions. This clinical study aimed to investigate interactions between edoxaban, a direct oral anticoagulant, and two traditional herbal medicines commonly used for stroke: Banhabaekchulcheonmatang (BBCT) and Hwangryeonhaedoktang (HRHDT). Korean healthy volunteers participated in a randomized, open-label, three-period, three-treatment, two-sequence clinical study. Treatments consisted of a single oral dose of edoxaban tablet (60 mg) in the presence or absence of multiple doses of BBCT or HRHDT three times daily for six days. Pharmacokinetic and pharmacodynamic parameters of edoxaban and its active metabolite M4 were assessed following administration of edoxaban alone or in co-administration with BBCT or HRHDT. When edoxaban was co-administered with BBCT or HRHDT, the area under the curve (AUC) of edoxaban remained unaffected. However, its peak concentrations (Cmax) were decreased by 18.5% to 28.1%. Similarly, co-administration of edoxaban with BBCT or HRHDT slightly decreased the AUC of M4 and reduced its Cmax by 16.8% to 27.1%. Results revealed that BBCT and HRHDT had a minor impact on pharmacokinetics of edoxaban and M4. Despite alterations in systemic exposures, all pharmacodynamic parameters of edoxaban derived from activated partial thromboplastin time and prothrombin time were equivalent irrespective of herbal medicine co-administration. These findings contribute to our understanding of potential interactions between conventional anticoagulants and traditional herbal medicines, highlighting the need for comprehensive evaluation in clinical practice.

Engineering implementation of permanent magnet uniform spreading system for 3 MeV electron beam accelerator

Electron radiation technology, a significant application of non-power civil nuclear technology, opens up various research opportunities for electron beam accelerators as radiation sources. This paper introduces the engineering implementation of a permanent magnet uniform spreading system for the 3 MeV electron beam accelerator. The system is designed to improve radiation homogeneity, which is a crucial performance parameter in the radiation processing. The paper firstly investigates the collimation of magnets and beam spot in electron beam accelerators and proposes a novel collimation method. In addition, we also address various engineering implementation challenges encountered during the practical application of the uniform spreading system's permanent magnet devices. As a prerequisite for the application of uniform spreading system, a long-term stability experiment is conducted on the permanent magnets in radiation environments. The engineering feasibility of the uniform spreading system is ultimately verified by assessing the radiation homogeneity at the target using radiation dose tablets.

Оценка эффективности нового лекарственного препарата Курс Успокоин таблетки для коррекции возрастных когнитивных нарушений у кошек

The treatment by Kurs Uspokoin tablets in a minimum initial daily dose of 7 mg/kg for the first three days, with a further increase to 14 mg/kg, showed a positive effect in correcting the behavior of older cats with progressive simptoms of cognitive disfunction. During the treatment were registered a statistically and clinically significant decrease in idiopathic vocalization, restoration of sleep cycles and wakefulness, elimination of house-soiling behavior, disorientation, increased activity, and improvement of social behavior. During the treatment by Kurs Uspokoin tablets and after its discontinuation no adverse reactions were registered.

A randomized, double-blind, placebo-controlled, dose-escalating phase IIa trial to evaluate the safety, tolerability, efficacy, and pharmacokinetics of multiple oral doses of Pynegabine tablets as add-on therapy in patients with focal epilepsy.

This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy. This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded. Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.

Disposition of Oral Nalbuphine and Its Metabolites in Healthy Subjects and Subjects with Hepatic Impairment: Preliminary Modeling Results Using a Continuous Intestinal Absorption Model with Enterohepatic Recirculation.

Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe hepatic impairment (Child-Pugh A, B, and C, respectively) compared to healthy matched subjects. NAL exposures were similar for subjects with mild hepatic impairment as compared to healthy subjects and nearly three-fold and eight-fold higher in subjects with moderate and severe hepatic impairment, respectively. Datasets obtained for healthy, moderate, and severe hepatic impaired groups were modeled with a mechanistic model that incorporated NAL hepatic metabolism and enterohepatic recycling of NAL and its glucuronidated metabolites. The mechanistic model includes a continuous intestinal absorption model linked to semi-physiological liver-gallbladder-compartmental PK models based on partial differential equations (termed the PDE-EHR model). In vitro studies indicated that cytochromes P450 CYP2C9 and CYP2C19 are the major CYPs involved in NAL oxidation, with glucuronidation mainly catalyzed by UGT1A8 and UGT2B7 isozymes. Complex formation and elimination kinetics of NAL and four main metabolites was well predicted by PDE-EHR. The model is expected to improve predictions of drug interactions and complex drug disposition.

Bioequivalence study of two formulations of afatinib dimaleate tablets in healthy subjects under fasting conditions: A randomized, open-label, single-dose, crossover trial.

To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles. This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit. Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC0-t, 90.26 - 105.52% for Cmax, and 93.49 - 104.05% for AUC0-∞. The 90% CI for the geometric mean ratios (test/reference) of Cmax, AUC0-t, and AUC0-∞ were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.

P-666 Comparison of IVF outcomes in women undergoing IVF stimulation using progestin primed ovarian stimulation (PPOS) Vs GnRH antagonist (GnRH-Antag) protocol

Abstract Study question Can PPOS achieve improved patient &amp; provider satisfaction while simultaneously blocking LH-surge, maintaining similar IVF outcomes like oocyte/embryo yield/clinical pregnancy rates(CPR) when compared to GnRH-Antag? Summary answer PPOS can achieve similar IVF outcomes as compared to GnRH-Antag protocol and is a patient friendly, cost-effective choice for ovarian stimulation without affecting oocyte/embryo yield/CPR. What is known already GnRH-Antag protocol is among the most widely used methods, as it blocks LH surge &amp; significantly lowers the risk of OHSS [Lambalk CB,2017]. However, this protocol has disadvantages like frequent monitoring, dose adjustment, high therapeutic cost and multiple injections[Ata B,2015]. PPOS successfully prevents ovulation and provides comparable IVFoutcomes (oocyte yield, blastocyst/euploid embryo rates, CPR) along with patient cost savings and increased convenience across all infertility diagnoses [Annalyn M.Welp, 2023]. It should be noted that most studies are non-randomized and comprise low to moderate-quality evidence. However, the consistency of the findings across different studies from different centres provides assurance in effect estimates. Study design, size, duration A retrospective cohort study conducted at a tertiary care fertility unit. Data for 449 women aged 21 to 40 years undergoing IVF stimulation using PPOS (n = 226) and GnRH-Antag (n = 223) protocol was retrieved from the hospital’s electronic database and analysed for a period between September 2022 to October 2023. Study population consisted of women undergoing freeze-all strategy either for lowering the risk of OHSS (hyper-responders) or for embryo pooling in view of very low ovarian reserve. Participants/materials, setting, methods For both groups either rFSH/rLH/HMG were used &amp; doses were indivisualised based on patient’s age, BMI &amp; ovarian reserve. PPOS group received twice daily dose of medroxyprogesterone acetate tablet(10 mg)/dydrogesterone(10 mg) from Day2 of cycle. GnRH-Antag group received Inj.Cetrorelix acetate (0.25 mg) daily as flexible protocol. Final oocyte maturation was induced with Triptorelin(0.2mg)/Choriogonadotropin alfa(250mcg)/both, once 2-3follicles reached 18-20mm. Transvaginal oocyte pick-up was performed 35-36h later. Women in PPOS group underwent freeze-all strategy followed by Frozen-Thawed Embryo-transfer. Main results and the role of chance Normally distributed continuous variables were compared using independent t-test, and categorical variables were compared by χ2 and Fisher’s exact test, where appropriate. Patient demographics, clinical/ovarian stimulation characteristics, embryological and IVF outcomes were compared for two groups. Patient demographics {Age(p-value:0.08), BMI(p-value:0.06), duration(p-value:0.09)/type(p-value:0.76) of infertlity}, total gonadotropin dose (p-value: 0.39) and duration of ovarian stimulation (p-value: 0.81) were comparable between the two groups. Though the mean LH level on trigger day was slightly higher in PPOS group (5.53 IU/L) than GnRH-Antag group (3.24 IU/L) (p-value: 0.02), statistically significant difference was not seen in the oocyte yield (p-value: 0.18), M-II oocytes (p-value: 0.17) &amp; fertilization rate (p-value: 0.23) in the two groups. The number of Day3 (p-value: 0.65), Day5 (p-value: 0.07) &amp; Day6 (p-value: 0.08) embryos available in the two groups were also comparable. IVF outcomes in terms of positive B-HCG result (p-value: 0.68), clinical pregnancy rate (p-value: 0.61) &amp; miscarriage rate (p-value: 0.27) showed no statistically significant difference in the two groups. Thus, we conclude that PPOS can achieve similar IVF outcomes as compared to the GnRH-Antag protocol, while at the same time proving to be patient friendly by reducing the need of multiple injection pricks, injection cost and the frequency of hospital visits. Limitations, reasons for caution This is a retrospective study and hence randomized comparison was not possible. PPOS can be used only when freeze-all strategy is planned, fresh embryo-transfer cannot be considered if need arises depending upon embryo quality. IVF service providers have to depend on patient compliance for using oral progestins to block LH-surge. Wider implications of the findings Study findings suggest that PPOS is a patient friendly and equally effective and safe IVF stimulation protocol when compared to GnRH-Antagonist. More RCT will be useful for investigating different aspects of PPOS (it’s utility for women with different ovarian reserve functions, conventional versus flexible approach, optimal dose of each progestin). Trial registration number Not applicable

Changes in lipid profiles of hypercholesterolemic rat (Rattus norvegicus) treated with iles-iles synbiotic effervescent tablets

Abstract The development of innovations in the use of functional food is growing, especially in the health sector. Synbiotic products are developed by combining prebiotics with probiotics. Synbiotic effervescent tablets provide prebiotic and probiotic compounds as supplements so they can be consumed and provide healthy effects. This study aims to determine the effect of giving synbiotic effervescent tablets from iles-iles tubers on lipid profiles and determine the lowest dose of synbiotic effervescent tablets in reducing cholesterol levels in blood rats. This study used the Randomized Complete Block Design as the experimental design, with a dose of tablet treatment 0.045 g/day/200 g rat body weight (half of normal dose), 0.09 g/day/200 g rat body weight (normal dose), and 0.18 g/day/200 g rat body weight (twice of normal dose). Rats given distilled water without being treated with tablets were used as controls. The lipid profiles (total cholesterol, triglycerides, HDL, and LDL) of the rats were measured after the treatment. Body weight changes were also monitored throughout the study. Treatment using synbiotic effervescent tablets at all doses for 28 days can lower total cholesterol, triglycerides, and LDL and increase HDL. The highest cholesterol reduction (49.94%) was found in rats given tablet doses twice the normal dose for 28 days.

Low-dose overlap initiation with split tablets of buprenorphine in intubated intensive care unit patients with opioid use disorder

BackgroundAs the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay.MethodsWe developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge.ResultsHere we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone.ConclusionInitiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.

Pharmacokinetics of a Fixed-Dose Combination Product of Amlodipine, Losartan, Ezetimibe, and Rosuvastatin and Its Comparison with Co-administration of Four Individual Components in Healthy Participants.

This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Pharmacokinetics and Bioequivalence of Two Formulations of Azithromycin Tablets: A Randomized, Single-Dose, Three-Period, Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Azithromycin is the first azalide antibiotic that is related to the macrolide family of antibiotics. Bioequivalence studies in China are initiated by the National Medical Products Administration (NMPA), which supports a generic consistency evaluation program for ensuring that generic products manufactured in China meet the required standards and provide equivalent therapeutic effects to their reference products. This study aimed to assess the bioequivalence of two azithromycin tablets under both fasting and fed conditions in healthy Chinese volunteers. This was a single-center, open-label, single-dose, randomized, three-way crossover trial with two independent groups (fasting group and fed group). A total of 72 healthy Chinese subjects (36 subjects in the fasting state and 36 subjects in the fed state) were enrolled and randomized to treatment. Blood samples were collected from 0 to 120 h after a single oral dose of a 250-mg generic azithromycin tablet (test, T) or branded azithromycin tablet (reference, R). The plasma concentrations of azithromycin were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS). A non-compartmental analysis method was used to estimate the pharmacokinetic parameters. Adverse events were documented. In a fasting state, the bioequivalence of maximum plasma concentration (Cmax) was evaluated using the reference-scaled average bioequivalence (RSABE) approach (within-subject standard deviation, SWR >0.294), and the bioequivalence of area under the concentration-time curve from time 0 to the time of the last measurable plasma concentration (AUC0-t) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) were evaluated by the average bioequivalence (ABE) method (SWR < 0.294). The geometric mean ratio (GMR) of T/R for Cmax was 106.49%, while the 95% upper confidence bound was < 0. The GMRs of AUC0-t and AUC0-∞ were 103.34% and 101.28%, and the 90% confidence intervals (CIs) of the test/reference were 95.90-111.35%/94.85-108.15%, respectively. In the fed state, the RSABE approach was applied to estimate the bioequivalence of Cmax (SWR >0.294), and the ABE approach was applied to estimate the bioequivalence of AUC0-t and AUC0-∞ (SWR < 0.294). The GMR for Cmax was 99.80%, while the 95% upper confidence bound value was < 0. The GMRs of AUC0-t and AUC0-∞ were 97.07% and 98.15%, and the 90% CIs of the T/R were 90.02-104.68% and 90.66-106.25%, respectively. All adverse events were mild and transient. The trial indicated that the test and the reference azithromycin tablets were bioequivalent and well tolerated in healthy Chinese volunteers under both fasting and fed conditions. Clinicaltrials, ChiCTR2300071630 (retrospectively registered in 19/05/2023).

Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

Quantification of isoniazid in tablets for tuberculosis treatment by thin layer chromatography with smartphone image capture and ImageJ analysis

Isoniazid (INH) oral dosage tablets are an antibacterial medication commonly used to treat tuberculosis (TB). While this medication can be highly effective in managing and curing TB, manufacturing of poor-quality INH products can lead to the proliferation of drug resistant TB strains – particularly in low- and middle-income countries (LMICs). It is therefore imperative that reliable methods of quality screening of INH tablets are available for areas that have limited access to traditional testing resources. In this study, a thin layer chromatography (TLC) procedure for INH identification is validated in conjunction with smartphone image capture and open-source image analysis software to provide an alternative quantitative quality screening method for INH tablets, primarily intended for applications in LMICs. The method assessed two individual tablet formulations: 100 mg and 300 mg INH, each from different manufacturers. The modified TLC procedure used for the study was based on a validated high-performance thin layer chromatography method for the determination of rifampicin, INH, and pyrazinamide in a fixed dosage tablet. Quantitation was performed by visualizing and photographing TLC plates using a UV lamp, 3D-printed light box, and Apple iPhone SE 2nd Generation (2020) and Google Pixel 4a (5G) smartphones, and images were then analyzed using ImageJ Fiji software. The processed images’ pixel data were used to create a calibration curve from the INH standard spots to determine the concentration of an INH sample spot. Linearity, range, accuracy, repeatability and intermediate precision, specificity, and robustness were evaluated. The method was linear in the range of 0.150–0.450 mg mL−1, with coefficients of determination ≥0.98. The overall accuracy of the method was 99.2 % with an RSD of 2.4 % for image sets captured using the Apple iPhone, and 99.7 % with an RSD of 3.3 % for image sets captured using the Google Pixel. The pooled standard deviations for repeatability and intermediate precision were 2.27 % and 3.25 %, respectively, for the iPhone and 2.62 % and 3.74 %, respectively, for the Pixel. The method demonstrated sufficient specificity and robustness. The results of this method validation suggest that this procedure may provide a feasible alternative to traditional testing as a low-cost means of quality screening in LMICs.

Оценка эффективности нового лекарственного препарата Курс Успокоин таблетки для коррекции возрастных когнитивных нарушений у кошек

The treatment by Kurs Uspokoin tablets in a minimum initial daily dose of 7 mg/kg for the first three days, with a further increase to 14 mg/kg, showed a positive effect in correcting the behavior of older cats with progressive simptoms of cognitive disfunction. During the treatment were registered a statistically and clinically significant decrease in idiopathic vocalization, restoration of sleep cycles and wakefulness, elimination of house-soiling behavior, disorientation, increased activity, and improvement of social behavior. During the treatment by Kurs Uspokoin tablets and after its discontinuation no adverse reactions were registered.

Quantitative determination of lobeglitazone sulfate and glimepiride in combined tablet by robust high‐performance thin layer chromatographic method

AbstractA combination of fixed dose tablet containing 0.5 mg lobeglitazone sulfate (LBZ) and 1 mg glimepiride (GLM) has demonstrated efficacy in enhancing glycemic control in diabetes. The projected work aimed to develop and validate a high‐performance thin‐layer chromatographic (HPTLC) methodology for the precise quantification of both the drugs in tablet formulations. The HPTLC analysis utilized aluminium plates layered with silica gel 60F254, and the solvent system consisted of ethyl acetate, benzene, and hexane (4:3:1 v/v/v) followed by densitometric scanning at 238 nm. The Rf value was found to be 0.68 ± 0.001 for LBZ and 0.48 ± 0.002 for GLM. The methodology exhibited linearity in the range of 100–2000 ng/band for LBZ and 200–4000 ng/band for GLM, with correlation coefficients of 0.9988 and 0.9981, respectively. Exceptional sensitivity was observed, with detection limits of 23.86 ng/band for LBZ and 58.26 ng/band for GLM, along with quantification limits of 72.32 ng/band for LBZ and 176.55 ng/band for GLM. The method demonstrated precision (% relative standard deviation of peak area &lt; 2) and accuracy (recovery between 97% and 102%). The suggested method is suitable for quantifying both the drugs in tablets, making it useful for routine quality control in laboratories.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study

ObjectivesWhile surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC.MethodsThis study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy.ResultsThere were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors “Postoperative TSH level ≥ 2 mU/L”, “Levothyroxine sodium tablet dose<1.4 µg/kg·d”, and “Combined with Hashimoto thyroiditis” were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05).ConclusionOptimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection.

The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.

Down-streaming Small-Scale Green Ammonia to Nitrogen-Phosphorus Fertilizer Tablets for Rural Communities

This study aims to evaluate the growth and production of sweet corn plants in response to the application of commercial NPK fertilizer and various doses of nitrogen-phosphorus fertilizer tablets. From early October 2022 to late January 2023, research was conducted at Research and Development Luas Birus Utama to produce nitrogen-phosphorus fertilizer tablets and at Research and Development Syngenta Indonesia Cikampek Station, Karawang, to perform a semi-field analysis. A factorial randomized block design with two treatment factors was employed in this study. The first factor was five types of nitrogen-phosphorus fertilizer tablets, namely, A (0% nitrogen and 6.3% phosphorus), B (0.81% nitrogen and 6.3% phosphorus), C (1.57% nitrogen and 6.1% phosphorus), D (2.33% nitrogen and 6.2% phosphorus), and E (3.06% nitrogen and 6.2% phosphorus). The second factor was F (standard nitrogen, phosphorus, and potassium). The results revealed that applying different dosages of nitrogen-phosphorus fertilizer tablets in combination with potassium chloride fertilizer yielded no different effect on the growth, biomass, and yield components of sweet corn plants when compared to applying NPK fertilizer. A comparison between the soil test results before and after application revealed that the formulation of fertilizers in tablet form helps plants to effectively absorb the required nutrients. It is currently possible to develop small-scale or microscale green ammonia production technology to fulfill the fertilizer requirements of rural communities because of its low cost, low carbon emissions, and low renewable energy consumption. The scarcity of fertilizer supplies endangers Indonesia’s food sustainability. Nitrogen-phosphorus fertilizer tablet production technology can be used in areas with a scarcity of inorganic fertilizers but with the potential for low-grade phosphate mines using commercial ammonia solutions. Thus, understanding how to produce nitrogen-phosphorus fertilizer tablets from ammonia solution will aid in the acceptance of microscale green ammonia production technology. Doi: 10.28991/ESJ-2024-08-02-016 Full Text: PDF

Zhilong Huoxue Tongyu capsule protects against atherosclerosis by suppressing EndMT via modulating Hippo/YAP signaling pathway

Background and aimZhilong Huoxue Tongyu Capsule (ZL capsule) has been demonstrated to be an effective and widely-used traditional Chinese medicine (TCM) formula for the treatment of various diseases, especially for atherosclerosis (AS) related cardiovascular and cerebrovascular diseases. Reversal of endothelial-mesenchymal transition (EndMT) plays a crucial role in the cure of AS. But the curative impact of ZL capsule on EndMT remains obscure during the development of AS. The purpose of this study is to explore the effect of ZL capsule on AS and to study the regulation mechanism on EndMT in AS by ZL capsule in vivo and in vitro. Experimental procedureAn in vivo model of AS was induced in ApoE−/− mice by administrating them with an 8-week period of high-fat diet (HFD). After oral gavage of different doses of ZL capsule and Atorvastatin calcium tablets (ATO) for 4 weeks, the lipid levels, plaque area, lipid deposition, and EndMT were evaluated using standard assays. In order to simulate EndMT in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoprotein (ox-LDL). Western blotting (WB) and immunofluorescence techniques were used to evaluate the intervention effect of ZL capsule on EndMT and Hippo/YAP pathways. Results and conclusionZL capsule demonstrated therapeutic effects on dyslipidemia and EndMT among atherosclerotic mice. To be specific, ZL capusle diminished the total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein (LDL-C) levels, whereas increased that of high-density lipoproteins (HDL-C). Meanwhile, ZL capusle upregulated the expression of endothelial markers (CD31 and VE-cadherin) and reduced that of mesenchymal markers (ɑ-SMA and FSP1), indicating that ZL capusle could inhibit EndMT during the development of AS. Furthermore, molecular docking results indicated that active ingredients including formononetin, calycosin, astragaloside III, astragaloside A in ZL capsule have strong affinity with YAP proteins, and ZL capsule can significantly repress the initiation of Hippo/YAP pathway during AS. In conclusion, ZL capsule effectively attenuated AS progression by exerting inhibitory effects on EndMT through modulation of the Hippo/YAP signaling pathway.