Tablet Dosage Research Articles

Surreptitious Administration of Disulfiram Along with Its Implantation Leading toDisulfiram-associated Encephalopathy: A Case Report

Disulfiram is a US FDA–approved medication for the management of alcohol use disorder. However, compliance with disulfiram has been the Achilles’ heel of its efficacy. Implantation and surreptitious administration of disulfiram are two methods occasionally used to ensure disulfiram compliance. We present the case of a 45-year-old man who underwent disulfiram implantation. Upon consuming his first drink after this procedure, his wife administered him a hefty dose of disulfiram tablets surreptitiously. The patient subsequently developed a state of fluctuating orientation, marked impairment in attention and concentration, dyscalculia, along with memory and motor deficits. The diagnostic dilemma associated with such a presentation, along with the ethical violations and medical risks associated with implantation and surreptitious use, is discussed. Disulfiram-associated encephalopathy is a rare consequence of disulfiram use and was precipitated in this patient by the administration of disulfiram using the above methods.

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

The use of the drug Kurs Uspokoin tablets in a minimum initial daily dose of 7 mg/kg for the first three days, with a further increase in the minimum daily dose to 14 mg/kg, showed a positive effect in correcting the behavior of dogs older than 10 years with progressive signs of cognitive impairment.

Pharmacokinetics and bioequivalence evaluation of two oral formulations of cotrimoxazole tablets in healthy Chinese volunteers under fasting conditions

This bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00–125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions.

Real-World evidence revelations: The potential of patient support programmes to provide data on medication usage.

Patient Support Programmes (PSPs) are used by the pharmaceutical industry to provide education and support to consumers to overcome the challenges they face managing their condition and treatment. Whilst there is an increasing number of PSPs, limited information is available on whether these programmes contribute to safety signals. PSPs do not have a scientific hypothesis, nor are they governed by a protocol. However, by their nature, PSPs inevitably generate adverse event (AE) reports. The main goal of the research was to gather all Novartis-initiated PSPs for sacubitril/valsartan, followed by research in the company safety database to identify all AE reports emanating from these PSPs. Core data sheets (CDS) were reviewed to assess if these PSPs contributed to any new, regulatory-authority approved, validated signals. Overall, AEs entered into the safety database from PSPs confirmed no contribution to CDS updates. Detailed review of real-world data revealed tablet splitting or taking one higher dose tablet a day instead of twice daily. This research, and subsequent analyses, revealed that PSPs did not impact safety label changes for sacubitril/valsartan. It revealed an important finding concerning drug utilisation i.e. splitting of sacubitril/valsartan tablets to reduce cost. This finding suggests that PSPs may contribute important real-world data on patterns of medication usage. There remains a paucity of literature available on this topic, hence further research is required to assess if it would be worth designing PSPs for collecting data on drug utilisation and (lack of) efficacy. Such information from PSPs could be important for all stakeholders.

Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration.

Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED). This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males. Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30and 60mg. The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1hour and mean terminal half-lives of 2.75and 3.26hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30to 60mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group. Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1hour before sexual intercourse in men with ED. This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED. Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30and 60mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration. CTR20192473 (http://www.chinadrugtrials.org.cn).

A Phase I Clinical Study of the Pharmacokinetics and Safety of Prusogliptin Tablets in Subjects with Mild to Moderate Hepatic Insufficiency and Normal Liver Function.

Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited. The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects. According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures. After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study. The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.

17-year study on the curative effect of treatment to prevent the recurrence of hepatitis B in different risk groups after liver transplantation

Objective: To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage. Methods: The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ(2) test between groups. Results: This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery (P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence (HR =181.92, 95%CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95%CI 1.289~20.889, P = 0.020), and a high dosage of HBIG (HR = 1.012, 95%CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion: High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.

Integration of sustainable chemistry frameworks with a single-pot, on-off fluorescence approach for enabling the facile quantification of mosapride; Application to pharmaceutical tablets and content uniformity

The twelve green chemistry concepts were considered for designing two new feasible, sensitive and selective spectroscopic approaches for the estimation of mosapride (MSP) in pure powder and tablet dosages. These approaches were derived from the reaction of the drug with erythrosine B in buffered acidic medium. The reaction yielded a binary complex, and its absorbance can be measured at its λmax (556 nm) while the incorporation of erythrosine B in the complexation reaction caused quantitative quenching of its native fluorescence that could be measured at 554 nm after excitation at 529 nm. The reaction parameters were carefully optimized for the two methods then the calibration curves were plotted. The absorbance and fluorescence quenching were directly proportional to MSP concentration in the ranges of 1.0–12.0 and 0.15–2.0 μg/mL, respectively. Limits of detection and quantitation were estimated giving values of 0.30 and 0.92 μg/mL for spectrophotometric method and 0.047 and 0.143 μg/mL for spectrofluorimetric method. In accordance with the International Council for Harmonization (ICH) guiding rules, the new methods were assessed proving their high accuracy, precision, and robustness. The methods were adopted for the determination of the cited drug in pharmaceutical tablets. Moreover, the uniformity of tablet contents was successfully tested according to USP utilizing the suggested approaches. Furthermore, the greenness of the suggested procedure was confirmed using three different approaches.

Therapeutic effect of an inhaled levodopa dry powder formulation on off episodes in patients with Parkinson’s disease

Background: Limited treatment options with a rapid onset of action are available to treat off episodes in Parkinson’s disease (PD) patients. Therefore, the development of rapid onset formulations, for instance with levodopa, is warranted, which was the reason to investigate an inhalable formulation of levodopa. Objectives: The primary objective was to determine the duration until maximum effect is reached of inhaled levodopa on the improvement of motor function of PD patients. The secondary objective was to compare the time until maximal effect and the maximal effect of inhaled levodopa versus oral levodopa. Design: Open-label randomized two-way one-period crossover trial. Methods: Nine PD patients in the ‘off state’ received one dose of inhaled levodopa (90 mg) from Cyclops® and one dose of levodopa orodispersible tablet (100 mg) on two consecutive days in a randomized order. A timed tapping test, Timed Up and Go test (TUG test) and Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III score were performed pre-dose and on set time points up to 90 min post-dose as measure for motor function. In addition, blood samples were taken for a pharmacokinetic evaluation ( Tmax, Cmax and area under the concentration time curve (AUC) 0–3 h). Results: The maximal effect of inhaled levodopa was reached at 30 min (tapping test), at 75 min (TUG test) and at 60 min (UPDRS III). The positive effect on the UPDRS was statistically significant within 20 min after inhalation. After oral administration, Cmax and AUC 0–3 h were found to be significant higher ( p = 0.028 and p = 0.028, respectively) than after pulmonary administration. Tmax was achieved significantly ( p = 0.028) faster after inhalation. The motor function examinations showed a similar maximum clinical improvement after pulmonary and oral administration and although not significant, inhaled levodopa results in a shorter median duration to maximum clinical effect for the TUG and timed finger-tapping test compared with oral administration (TUG: inhalation 55.0 and oral 67.5 min, timed finger-tapping test: inhalation 35.0 and oral 57.5 min). After the levodopa inhalation, there were no adverse events observed and no significant differences found in long-function parameters. Conclusion: Inhaled levodopa from Cyclops® shows promising data as a rescue therapy for PD patients with off episodes, not responsive to the current oral therapies. Trial registration: The study protocol was approved by the local ethics board ‘Regionale toetsingscommissie patiëntgebonden onderzoek’ (RTPO) in Leeuwarden, The Netherlands (approval number RTPO1019). The study was registered in in the Dutch trial register (LTR) with identification number NL6876. From 5 March 2024 on, the research data on onderzoekmetmensen.nl are known as ‘Overview of Medical Research in the Netherlands’ (OMON). This means the use of the name LTR has thus been dropped. Now, it is registered in the OMON with the same identification number (NL6876, Effectiveness of inhaled levodopa in PD | Research with human participants (onderzoekmetmensen.nl)). All patients provided written informed consent.

Comprehensive Analysis of Phytoestrogens Intervention in Osteoporosis Management: A Systematic Review of Randomized Controlled Trials

Introduction: Osteoporosis is a medical condition characterized by increased bone turnover and decreased bone mass, which leads to bone fractures. Antiresorptive therapy, hormone replacement therapy (HRT), and bisphosphonates are used as first-line therapy related to numerous side effects. The osteoprotective properties of phytoestrogens are well known. This systematic review aims to explore the potential of phytoestrogen in the management of osteoporosis patients based on serum bone biomarker analysis. Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD) and other serum bone biomarkers. Various forms of phytoestrogen intervention were used, including isoflavone extracts with an administered dose (tablets, capsules), genistein extract (tablets), resveratrol, and isolated soy protein (IBS) in powder form, beverages, food and snacks, and soy products. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Ten articles were included in the systematic review. Results: Seven studies found the mean changes in BMD values were significantly higher than the control group's after phytoestrogen intervention. Phytoestrogens dramatically boost numerous bone formation markers, including calcium, phosphorus, Ca/P ratio, and vitamin D, followed by a drop in BAP and osteocalcin levels. Phytoestrogens dramatically increased numerous bone formation markers, including calcium, phosphorus, Ca/P ratio, and vitamin D, followed by a decrease in BAP and osteocalcin levels. Furthermore, intervention may reduce bone resorption indicators such as CTX, RANKL, AKP, OPG, DPD, and PTH. Conclusion: Phytoestrogen intervention has demonstrated effectiveness in increasing bone mineral density and serum bone biomarkers.

Comparative Pharmacokinetic Studies of One‐Month Donepezil IM Depot and Once Daily Oral Tablet in Healthy Male Volunteers

AbstractBackgroundThis study is to evaluate the safety and tolerability of single dose of one‐month donepezil IM depot (GB‐5001) in healthy male volunteers and to compare pharmacokinetic parameters of 70mg donepezil IM depot and 10mg once daily oral tablet (Aricept®) in human.MethodIn this phase 1, a randomized, double‐blind, placebo‐controlled, dose‐escalation study, 48 healthy subjects were randomized to single dose of Aricept tablet or placebo or GB‐5001 (70mg or 140mg or 280mg) for 64 days. In this study, safety and tolerability of 70mg donepezil IM depot were examined by monitoring adverse events and vital signs. PK parameters such as AUCt, AUCinf, Cmax and Tmax were compared by measuring donepezil concentration after a single dose of 70mg IM depot and 10mg oral tablet.ResultA single dose of 70mg donepezil IM depot showed no significant adverse events and was well tolerated in healthy male volunteers. In 70mg GB‐5001, all the subjects had measurable concentrations up to 1512 h post dose. The geometric mean of PK exposure parameters are 6482.82 h*ng/mL, 6604.01 h*ng/mL and 11.40 ng/mL for AUCt(0‐1512h), AUCinf, and Cmax, respectively. The median peak concentration (Tmax) was observed at 432h post dose. In 10mg oral Aricept, all the subjects had measurable concentrations up to 240 h post dose. The geometric mean of PK exposure parameters are 656.84 h*ng/mL, 751.34 h*ng/mL and 17.68 ng/mL for AUCt(0‐240h), AUCinf, and Cmax, respectively. The median peak concentration (Tmax) was observed at 2.25 h post dose.ConclusionA single dose of 70mg donepezil IM depot was found to be safe and well tolerated in healthy male volunteers. The pharmacokinetic results of 70mg donepezil IM depot showed stable donepezil blood concentration for more than one month without burst drug release, and showed comparable unit dose drug exposure not lower than that of once daily 10mg oral formulation. Through the PK results for additional higher doses and multiple PK simulations, optimal once monthly dose of donepezil IM depot could be suggested which will be bioequivalent to 10mg once daily tablet.

Bioequivalence of 240mg Apalutamide Tablets and Preparation in Aqueous Food Vehicles for Alternative Administration.

A 240-mg single tablet has been developed with the focus of reducing the pill burden of the apalutamide daily dose of 240mg (4×60-mg tablets). An open-label, randomized, single-dose phase 1 study with a 2-sequence and 2-period crossover design in healthy men determined the bioequivalence of a 240-mg single tablet versus the currently available 4×60-mg tablets (Part 1, N = 74) and assessed effect of a high-fat meal (Part 2, N = 21) on apalutamide maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-72h). The 90% confidence interval of geometric mean ratios for Cmax and AUC0-72h fell between 80% and 125% for both Part 1 and Part 2. No new safety concerns with the 240-mg single tablet were observed. To support the use of different food vehicles as well as nasogastric (NG) tubes for alternative administration, we conducted in vitro compatibility studies to evaluate the purity, dose, and stability of 240-mg tablets dispersed in applesauce/yogurt/orange juice/green tea as well as in NG tubes (polyurethane/silicone/polyvinyl chloride). The studies confirmed the alternative administrations do not affect the purity, dose-accuracy, or stability of apalutamide. The apalutamide 240-mg tablet is bioequivalent to 4×60-mg tablets and compatible with the tested food vehicles and NG tubes.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

BIOEQUIVALENCE OF METFORMIN AS AN ORAL ANTIDIABETIC: A SYSTEMATIC REVIEW

Metformin is the first line in type 2 Diabetes Mellitus (DM). Metformin is available as an innovator drug and copy drug. The high price of innovator drugs makes it difficult for patients to obtain the required drugs. Therefore, many pharmaceutical industries have developed a copy of the innovator drug. To obtain .a distribution license, the pharmaceutical industry must conduct a bioequivalence test on metformin copy tablets to ensure that the copy drug has the same efficacy, safety, and quality as the innovator drug. However, several surveys show that most patients believe that the effectiveness of copy drugs is not equivalent to the innovator drug. This study aims to determine the bioavailability profile and bioequivalence profile of Metformin copy tablets to Glucophage® (Merck) innovator tablets so that it can provide an overview of the effectiveness of copy drugs with innovator drugs and the public no longer hesitate to use copy drugs. Metformin copy tablets are declared bioequivalent to the innovator drug if they provide a Confidence Interval (CI) value of 90% in the 80-125% range. All 500 mg, 850 mg, and 1000 mg doses of metformin copy tablets, both fasting and eating conditions, gave bioequivalent results to the innovator Glucophage® based on 90% CI.

SAT595 A Successful Long-time Experience Of A Dose-finding Approach For The Treatment Of Central Adrenal Insufficiency (CAI) With Prednisone

Abstract Disclosure: P.F. Santos-Neto: None. S.R. Correa-Silva: None. B.M. Mascarenhas Nakano: None. J. Abucham: None. Introduction: In patients with CAI, hydrocortisone (HC) is considered the preferred treatment. Recommended daily doses are based on estimates of daily cortisol production which have recently been decreased. Doses in the upper part of the previously suggested range have been associated with higher cardiovascular morbimortality. Currently recommended HC replacement doses have been reduced. In our country, HC has never been commercially available in tablets, but prednisone, an intermediate action glucocorticoid available in 5mg and 20mg tablets (lower doses are available elsewhere) is easily found, at low cost, and doesn't need prescription. Aim: To analyze our experience with prednisone in patients with CAI using the same dose-finding protocol established four decades ago. Patients: Data were extracted from electronic files. After applying inclusion/exclusion criteria, 72 out of 96 patients entered the study. Inclusion criteria: &amp;gt;18y, last consultation &amp;lt;2y, stable and same daily doses of prednisone, stable replacement of thyroid and sex hormone deficits in the last year. Exclusion criteria: Cushing´s disease, alternating prednisone doses, non-controlled acromegaly, intestinal malabsortion, other diseases requiring glucocorticoid, hepatic insufficiency. Dose-finding Protocol: Starting doses of prednisone in outpatients are usually 2.5mg or 5.0mg. Thereafter, dose adjustments are done according to clinical signs and symptoms and a pre-defined minimal dose of 2.5mg is attempted in all patients. Patients requiring &amp;gt;2.5mg are changed to 5.0mg, and then suggested to decrease to 3.75mg (3/4 of a 5.0mg tablet). If 3.75mg doses are judged insufficient, we return to 5.0mg; if unpractical, we suggest to alternate doses or to return to 5.0mg. Statistical Analysis: Patients were divided in two groups according to the prednisone daily dose. Group comparisons: Student´s t-test and Fisher´s exact test. P&amp;lt;0.05 was set as significant. Results: Fifty-four patients were on 2.5mg (75%) and 18 patients were on 5.0mg (25%) of prednisone. None was on GH replacement. The 5mg group tended to be younger (P=0.06). No significant differences (0.10&amp;lt;P&amp;lt;1.0) were found in relation to sex, treatment duration, BMI (both at diagnosis and last visit), other hormone deficiencies, IGF-1 levels, diabetes mellitus, dyslipidemia, and hypertension between the two groups. Conclusions: Adult patients with CAI are successfully treated with a single daily morning dose of prednisone determined by a dose-finding approach. In the absence of GH replacement, most patients stay at 2.5mg and the remaining ones at 5.0mg. The lack of difference between doses in parameters of excessive glucocorticoid exposure indicates that our approach is able to adjust prednisone doses close to individual requirements. A broader range of doses from &amp;lt;2.5mg including intermediate doses &amp;lt;5mg should be tried if low dose tablets are available. Presentation: Saturday, June 17, 2023

Development and Application of a Validated HPLC Method for the Determination of Alpelisib and its Process-Related Impurities in Pure Drug and Pharmaceutical Formulations

Impurity analysis plays a significant role in the manufacture of a safe pharmaceutical product that ensures the safety of consumers. Keeping this in consideration, the present study was intended to develop a simple and sensitive HPLC method for the resolution and quantification of 4 process-related impurities namely impurities 1, 2, 3 and 4 in alpelisib pure drug and formulations. The method consumes greener solvents as a mobile phase that resolves the analytes on ProntoSIL ODS-C18 (250×4.6 mm; 5 μ id) column at room temperature as stationary phase, ethanol and 0.1% aqueous acetic acid in 65:35 (V/V) at pH 4.5 as mobile phase at 0.8 mL/min flow rate, UV detection at 246 nm. The method can detect the analytes at retention times of 7.05, 4.52, 6.09, 2.88 and 8.14 min respectively for alpelisib, impurity 1, 2, 3 and 4. The analysis was completed with a run time of 15 min that consume less solvent and the same analysis time. The linearity of the proposed method was perceived in the range of 12.5 to 100 μg/mL for alpelisib and 0.0125 to 0.10 μg/mL for impurities. The method can effectively resolve the unknown stress degradation products generated during the stress exposure of alpelisib along with its known impurities in the study. The outcomes of other validation studies were likewise satisfactory and proven adequate for regular analysis of alpelisib and its process-related impurities in bulk drug and pharmaceutical tablet doses.

Level and factors associated with compliance to iron-folic acid supplementation among pregnant women in rural Soro district, Hadiya Zone, Ethiopia: cross-sectional study

BackgroundDespite the advantages of iron and folic acid supplementation, the compliance status among pregnant women for the supplements is very low in Ethiopia. However, the factors found to be associated with the compliance of iron and folic acid supplementation varies depending on geographical locations and socio-cultural characteristics within the country. Therefore, this study assessed the compliance to iron and folic acid supplements and its associated factors among pregnant women in the rural Soro district, Hadiya Zone, Southern Ethiopia.MethodsCross-sectional study design was applied to conduct the study. The total sample size was 274. This study was conducted from June 10 up to 20, 2018. Women who live in rural Soro district at least for 6months and gave live birth 12 months prior to the survey were included in the study. The study subjects were selected by applying the simple random sampling method. Independent variables with p-value less than or equal to 0.25 during bivariate analysis were candidate for multivariable analysis. Finally, during multivariable analysis the independent variables with P-value less than 0.05 were declared as factors significantly associated with compliance to iron-folic acid supplementation during pregnancy.ResultsOf the whole study participants only 51(18.8%) women had taken iron folic acid supplements for at least 90 days during their last pregnancy. Women who had frequent visits to health facilities for ante natal care were more likely to be compliant with iron-folic acid supplements than their counterparts [AOR(95%CI) = 4.50(1.18, 17.14)].ConclusionIn this study, the higher proportion of pregnant women did not take adequate dose of iron and folic acid tablets during their last pregnancy. Women who had a frequent visit to health facilities for antenatal care were more likely to be compliant for iron folic acid supplements than their counterparts. Every effort should be made in the community and health facilities by concerned bodies working in the maternal health area to mobilize pregnant women to take the antenatal care for at least four times to achieve the minimum dose of iron and folic acid supplements.

Low-dose apatinib in subjects with renal impairment: A pharmacokinetics study

ObjectiveIn patients with renal impairment, we studied apatinib and its major metabolites (M1–1, M1–2, M1–6, and M9–2) for pharmacokinetics. MethodsSubjects with different renal functions were given a single oral dose of apatinib mesylate tablets of 250 mg. Pharmacokinetic samples were collected at 1 hour before dosing,0.25, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, and 96 h after dosing. The pharmacokinetic parameters of apatinib and its major metabolites were calculated by noncompartmental analysis. ResultsComparing PK parameters of the mild or moderate renal impairment group with the healthy group: the geometric mean ratios of maximum observed drug concentration (Cmax), the area under the plasma drug concentration-time curve from time 0 to the final quantifiable time (AUC0-t), and the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0–inf) were all about one. No significant effect of mild and moderate renal impairment on apatinib pharmacokinetics was observed. Mild and moderate renal impairment was also not observed to have a significant effect on the pharmacokinetics of metabolites M1–1, M1–2, and M1–6. However, mild and moderate renal impairment had a certain increase in exposure to the metabolite M9–2. Considering that M9–2 has no inhibitory effect on protein tyrosine kinase, it has no clinical significance. In addition, the proportion of cumulative excretion of apatinib and its major metabolites was small and almost negligible in all three groups of subjects. ConclusionPatients with mild and moderate renal impairment do not need to adjust the dose of apatinib when using low dose (250 mg) apatinib.

Increase in Deltoid Compartment Pressures Immediately After Arthroscopic Rotator Cuff Repair Does Not Significantly Affect Postoperative Opioid Consumption

To investigate the association between changes in individual (anterior, lateral, and posterior) and overall deltoid compartment pressures and postoperative opioid consumption up to 14 days after primary double-row arthroscopic rotator cuff repair (ARCR). In 113 consecutive patients undergoing primary double-row ARCR, anterior, lateral, and posterior deltoid compartment pressures were measured prior to incision and immediately after closure with a manometer. Postoperatively, all patients were provided with an identical rehabilitation protocol, quantity and dose of opioid tablets, and pain journal in which to record daily opioid consumption and visual analog scale pain scores for 14 days after surgery. The pain journals were collected at the first postoperative visit, and opioid consumption was calculated based on morphine equivalents. Statistical analysis was performed to determine the association between deltoid compartment pressures and opioid consumption postoperatively. Sixty-nine percent of patients who met the inclusion criteria (74 of 107) returned the pain journals. The mean age at the time of surgery was 57.4 ± 8.8 years (range, 30-75 years), with female patients being significantly older (P= .03). The mean length of surgery was 71.7 ± 16.3 minutes. No significant association between increase in individual (anterior, lateral, or posterior) or mean overall compartment pressures and morphine equivalents of opioid consumption was appreciated on any postoperative day. No significant correlation between increase in individual or overall deltoid compartment pressures after ARCR and postoperative opioid consumption in the immediate postoperative period was found in this study. Level II, prospective cohort study.

The Art of Dosing for Subcutaneous Immunotherapy in North America

Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.