Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

BACKGROUND: Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. METHODS: Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. RESULTS: Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. CONCLUSIONS: A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT04574362 Date registered: 2020-10-05.

Drug-induced Stevens-Johnson syndrome in Post traumatic facial injury.

Stevens-Johnson syndrome is a severe adverse drug reaction affecting the skin and mucous membrane. The causes include Sulfonamides, Anticonvulsants, etc. A patient developed ulcerations in the lips and oral cavity with difficulty in swallowing and rashes over the back, abdomen, and genitalia following administration of injection ceftriaxone 1 g intravenous (IV) b.i.d, injection pantoprazole 40 mg IV b.i.d, tablet aceclofenac + paracetamol 325 mg b.i.d, tablet cetirizine 10 mg b.i.d, chlorhexidine mouth wash, and injection metronidazole 500 mg IV t.i.d for the treatment of traumatic facial injury after 4 days of treatment. Injection ceftriaxone and tablet aceclofenac + paracetamol were suspected as the cause of this reaction. The two drugs were stopped. The patient was treated with corticosteroids, other antimicrobials, and oral topical anesthetics. Health-care providers should be careful about the possible adverse drug reactions even to commonly used drugs.

Acupotomy combined with metformin hydrochloride tablet for type 2 diabetes mellitus and its effect on serum inflammatory factors. / é’ˆåˆ€è”åˆç›é ¸äºŒç”²åŒèƒç‰‡æ²»ç–—2åž‹ç³–å°¿ç— çš„ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ ç‚Žæ€§å› å­å«é‡çš„å½±å“.

OBJECTIVES: To observe the clinical efficacy of acupotomy combined with metformin hydrochloride tablet for type 2 diabetes mellitus (T2DM) and its effect on serum levels of inflammatory factors. METHODS: A total of 68 patients with T2DM were randomized into an acupotomy group (34 cases, 2 cases dropped out) and a western medication group (34 cases, 2 cases dropped out). Metformin hydrochloride tablet was given orally in the western medication group, 0.5-1 g each time, twice a day, for continuous 8 weeks. On the basis of the treatment in the western medication group, acupotomy was applied at bilateral Geshu (BL 17), Weiwanxiashu (EX-B 3), Ganshu (BL 18) in the acupotomy group, once a week for continuous 8 weeks. Before and after treatment, in the two groups, blood glucose (fasting blood glucose [FBG], 2-hour plasma glucose [2 h PG] and glycosylated hemoglobin [HbA1c]), TCM syndrome score, blood lipids (total cholesterol [TC], triglyceride [TG], low density lipoprotein cholesterol [LDL-C] and high density lipoprotein cholesterol [HDL-C]), insulin (fasting insulin [FINS] and 2-hour insulin [2 h INS]), C-peptide indexes (fasting C-peptide [FC-P] and 2-hour C-peptide [2 h C-P]), dosage of metformin hydrochloride tablet and diabetes specific quality of life (DSQL) score were observed, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17 were measured by ELISA. RESULTS: After treatment, the FBG, 2 h PG, HbA1c, TCM syndrome scores, TC, TG, LDL-C, FINS, 2 h INS, FC-P, 2 h C-P, DSQL scores as well as the serum levels of TNF-α, IL-6, IL-17 were decreased compared with those before treatment (P<0.01), HDL-C was increased compared with that before treatment (P<0.01) in the two groups; the dosage of metformin hydrochloride tablet was decreased compared with that before treatment in the acupotomy group (P<0.01). After treatment, in the acupotomy group, the FBG, HbA1c, TCM syndrome score, TC, TG, LDL-C, FINS, 2 h INS, FC-P, 2 h C-P, dosage of metformin hydrochloride tablet, DSQL score as well as the serum level of TNF-α were lower than those in the western medication group (P<0.05). CONCLUSIONS: Acupotomy combined with metformin hydrochloride tablet can improve the blood glucose, clinical symptoms and quality of life in patients with T2DM, its mechanism may be related to the regulation of inflammatory reaction.

Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

Phase II study investigating the efficacy and safety of glesatinib (MGCD265) in patients with advanced NSCLC containing MET activating alterations.

OBJECTIVES: Dysregulated signaling by mesenchymal epithelial transition factor (MET) and heightened AXL activation are implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Glesatinib (MGCD265) is an investigational, oral inhibitor of MET and AXL. MATERIALS AND METHODS: This open-label, Phase II study investigated glesatinib (free-base suspension [FBS] capsule 1050 mg BID or spray-dried dispersion [SDD] tablet 750 mg BID) in patients with advanced, previously treated NSCLC across four cohorts grouped according to presence of MET activating mutations or amplification in tumor or ctDNA. The primary endpoint was objective response rate (ORR). RESULTS: Sixty-eight patients were enrolled: n = 28 and n = 8 with MET exon 14 skipping mutations in tumor tissue and ctDNA, respectively, and n = 20 and n = 12 with MET gene amplification in tumor tissue and ctDNA, respectively. Overall, ORR was 11.8 %, median progression-free survival was 4.0 months, and median overall survival was 7.0 months. Among patients with MET activating mutations, ORR was 10.7 % with tumor testing and 25.0 % with ctDNA testing. For MET amplification, responses were observed only in patients enrolled by tumor testing (ORR 15.0 %). Diarrhea (82.4 %), nausea (50.0 %), increased alanine aminotransferase (41.2 %), fatigue (38.2 %), and increased aspartate aminotransferase (36.8 %) were the most frequent adverse events assessed as related to study medication. Glesatinib exposure was similar with the SDD tablet and FBS capsule formulations. The study was terminated early by the sponsor due to modest clinical activity. CONCLUSIONS: Glesatinib had an acceptable safety profile in patients with advanced, pre-treated NSCLC with MET activating alterations. Modest clinical activity was observed, which likely reflects suboptimal drug bioavailability suggested by previously reported Phase I data, and pharmacodynamic findings of lower than anticipated increases in circulating soluble shed MET ectodomain (s-MET).

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.

Evaluation of caffeic acid mucoadhesive tablets on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Oral aphthous stomatitis is a chronic inflammatory condition. Numerous medications have been investigated to treat the symptoms of the disease. However, these days patients prefer herbal medicines due to lower side effects. Considering the anti-inflammatory, analgesic, and anti-oxidant properties of Caffeic acid and its few side effects, the aim of this study was to assess the impact of Caffeic acid on recurrent aphthous stomatitis (RAS). investigating the effect of caffeic acid mucoadhesive tablets on the size and pain intensity of the aphthous lesions. METHODS: in this double-blinded clinical trial study, 47 patients who met the inclusion criteria were selected by convenient sampling method. The patients were assigned to two groups randomly; the control group (placebo recipients) and the intervention group (Caffeic acid recipients). Patients were followed up for 7 days following the intervention. The diameter of the inflammatory lesion was measured in millimeters, and the pain intensity was recorded based on the VAS scale (Visual Analogue Scale). This trial was approved by the medical ethics committee of Mazandaran University of Medical Sciences (Ethical code: IR.MAZUMS.REC.1401.261) and received IRCT code of IRCT20220815055700N1on 03/09/2022. RESULTS: the diameter of the lesion in both groups decreased over time, and there was no significant difference between the intervention and control groups, except on the fifth day when the diameter of the lesion was significantly greater in the control group (P = 0.012). From the second day, the control group's average pain intensity was significantly higher than the intervention group's pain intensity (P < 0.05). CONCLUSIONS: when comparing mucoadhesive tablets containing Caffeic acid and placebo, the findings demonstrated that Caffeic acid has a significant efficacy in reducing aphthous lesions' diameter and pain intensity of the patients and are suggested for palliative oral aphthous lesions treatment since they showed significant anti-inflammatory and analgesic effects on recurrent aphthous stomatitis.

Treatment of Helicobacter Pylori Infection and the Colonization of the Gastrointestinal System by Resistant Bacteria.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infections are widely treated with antibiotic regimens such as "Amoxicillin 1 gr 2 × 1 tablet, Clarithromycin 500 mg 2 × 1 tablet, and Lansoprazole 30 mg 2 × 1 tablet" for 14 days. We conducted a prospective observational study to explore whether this treatment protocol serves as a predisposing factor for the colonization of resistant gastrointestinal microflora, namely vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase Enterobacterales (ESBL-E), and carbapenem-resistant Enterobacterales (CRE). MATERIALS AND METHODS: Pre- and post-treatment stool samples from 75 patients diagnosed with H. pylori, without a prior treatment history, were cultured and evaluated based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Of the 75 evaluated patients, a pronounced surge in ESBL-E positivity was observed. Before initiating antibiotic treatment, 12 patients (16%) had ESBL-E-positive strains in their gastrointestinal tract. Notably, this number surged to 24 patients (32%) after the conclusion of the 14-day treatment regimen. The change was statistically significant, with a P value of less than 0.002, indicating a clear association between treatment for H. pylori and heightened ESBL-E colonization. Notably, VRE and CRE remained undetected in patients throughout the study, suggesting that the treatment regimen may specifically amplify the risk of ESBL-E colonization without affecting VRE and CRE prevalence. CONCLUSIONS: As the inaugural report from Turkey on this issue, our study suggests that antibiotic regimens for H. pylori eradication contribute to the increased risk of ESBL-positive bacterial colonization in the gastrointestinal tract.

A review of amphetamine extended release once-daily options for the management of attention-deficit hyperactivity disorder.

INTRODUCTION: Amphetamine preparations are one of the two categories of stimulant medications approved for the treatment of attention deficit hyperactivity disorder (ADHD). Optimal treatment of ADHD aims to reduce core symptoms for as much of the waking hours as possible, leading to longer-acting delivery formats. In addition, the pediatric population commonly has difficulty swallowing pills and manufacturers have developed a variety of options to facilitate this concern. These include chewable tablets, capsules that may be sprinkled on soft food, liquids and transdermal patches. AREAS COVERED: This article reviews the once-daily extended-release preparations currently available for amphetamine compounds, their pharmacodynamics, and common adverse effects. EXPERT OPINION: There is an extensive evidence base supporting use of amphetamine preparations in the treatment of ADHD. Rapid onset of action and a favorable side effect profile make these widely used. The availability of once-daily extended-release chewable tablets, capsules that can be opened and sprinkled, and liquid formulations provides clinicians with multiple options to meet the specific needs of patients with difficulty swallowing whole pills.

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Salivary Amylase-Responsive Buccal Tablets Wipe Out Chemotherapy-Rooted Refractory Oral Mucositis.

Oral mucositis (OM) is the most common and refractory complication of cancer chemotherapy and radiotherapy, severely affecting patients' life quality, lowering treatment tolerance, and discouraging patient compliance. Current OM delivery systems mostly affect the comfort of patient use and lead to poor compliance and unsatisfactory effects. Herein, salivary amylases (SAs)-responsive buccal tablets consisting of porous manganese-substituted Prussian blue (PMPB) nanocubes (NCs), anti-inflammatory apremilast (Apr) and starch controller have been engineered. PMPB NCs with large surface area can serve as carriers to load Apr, and their multienzyme-mimicking activity enables them to scavenge reactive oxygen species (ROS), which thus synergize with Apr to mitigate inflammation. More significantly, the starch controller can respond to abundant SAs in the oral cavity and realize the cascade, continuous, and complete drug release after enzymatic decomposition, which not only aids with high tissue affinity to prolong the resistance time but also improves the comfort of use. The preclinical study reveals that contributed by the above actions, such buccal tablets mitigate inflammation, promote endothelium proliferation and migration, and accelerate wound healing for repressing chemotherapy-originated intractable OM with positive oral microenvironment and shorter recovery time, thus holding high potentials in clinical translation.

Secondary cytoreductive surgery followed by olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent ovarian cancer: A multi-center retrospective study.

OBJECTIVE: To evaluate the effect of secondary cytoreductive surgery (SeCRS) followed by platinum-based chemotherapy (PBC) and olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent epithelial ovarian cancer. METHODS: This was a retrospective study of a prospective database. We collected information on 623 patients diagnosed with BRCA mutated recurrent epithelial ovarian cancer, all of whom underwent SeCRS followed by PBC in combination with or without olaparib. Overall survival and progression-free survival were measured to evaluate treatment effectiveness. RESULTS: Of the 623 patients recruited, 240 underwent SeCRS plus hyperthermic intraperitoneal chemotherapy followed by PBC and olaparib maintenance therapy (Group A), 248 underwent SeCRS followed by PBC and olaparib maintenance therapy (Group B), and 135 underwent SeCRS followed by PBC only upon recurrence (Group C). The median progression-free survival for Group A was significantly longer than that for Group B (32.5 vs. 24.2 months, P<0.001), and Group B was significantly longer than Group C (24.2 vs. 15.1 months, P<0.001). The median overall survival for Groups A was significantly longer than that for Group B (71.4 vs. 63.5 months, P<0.001), and Group B was significantly longer than Group C (63.5 vs. 47.5 months, P<0.001). CONCLUSIONS: This study suggested that SeCRS followed by PBC and olaparib maintenance therapy resulted in longer overall survival and progression-free survival than SeCRS followed by PBC only in patients with BRCA mutated recurrent ovarian cancer, especially in patients treated with SeCRS plus hyperthermic intraperitoneal chemotherapy.

Factors associated with the acceptability of Lopinavir/Ritonavir formulations among children living with HIV/AIDS attending care and treatment clinics in Mbeya and Mwanza, Tanzania.

INTRODUCTION: Children living with chronic illnesses are offered formulations based on manufacturer and distributor research. The aim of this study is to better understand the perspectives of children and their caregivers in accepting Lopinavir/ritonavir (LPV/r) formulations. METHODS: 362 participants were recruited from two pediatric HIV/AIDS clinics in Mbeya and Mwanza, Tanzania, from December 2021 to May 2022. A translated questionnaire was piloted and validated at both clinics, followed by the implementation of a cross-sectional study. RESULTS: 169 participants (47.1%) reported general difficulties in swallowing, regardless of formulation, while 34.3% and 38.5% reported vomiting tablets and syrups, respectively. Statistical significance is shown to support that children can swallow medications if they can eat stiffened porridge (Ugali). This correlated with the lower incidence of younger children being able to swallow compared to older children (above six years of age). Children older than six years preferred taking tablets (independent of daily dosage) better than other formulations. Significantly, older children who attend school were associated with high odds of swallowing medicine (AOR = 3.06, 95%CI; 1.32-7.05); however, age was not found to be statistically related to ease of administration for Lopinavir/Ritonavir in this study. CONCLUSIONS: Lopinavir/Ritonavir tablets remain the most accepted formulation among children and adolescents with HIV/AIDS. This study highlights the impact of various factors affecting the acceptability of pediatric formulation, suggesting that children younger than six years, unable to eat Ugali and not attending schools may be most vulnerable regarding their ability to accept Lopinavir/Ritonavir formulations. Further studies are needed to assess the acceptability of other medications in chronically ill children.

Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies.

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.

Analysis on the therapeutic effect of Cangfu Daotan Decoction combined with drospirenone and ethinylestradiol tablets (II) on patients with polycystic ovary syndrome.

OBJECTIVE: This study was designed to investigate the therapeutic effect of Cangfu Daotan Decoction (CDD) combined with drospirenone and ethinylestradiol tablets (II) on patients with polycystic ovary syndrome (PCOS). METHODS: Patients with PCOS were gathered from September 2020 to September 2022 and divided into the experimental group (n = 36), treated with CDD combined with drospirenone and ethinylestradiol tablets (II), and the control group (n = 41), received only drospirenone and ethinylestradiol tablets (II). Levels of sex hormone, obesity, blood glucose, blood lipid were detected and compared between the two groups pre- and post-treatment. The treatment efficacy, Traditional Chinese Medicine (TCM) syndrome score, adverse drug reactions, and pregnancy rate were compared as well. RESULTS: After treatment, the experimental group had a higher treatment efficacy (94.44% vs 73.17%, P < 0.05) and a higher pregnancy rate (44.44% vs 21.95%, P < 0.05) than the control group, but the difference in the incidence of adverse drug reactions was not statistically significant (P > 0.05). Compared with control group, TCM syndrome score and levels of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and waist circumference of the experimental group after treatment displayed remarkable reduction (P < 0.05), while the levels of estradiol (E2) and high-density lipoprotein cholesterol (HDL-C) showed a remarkable increase (P < 0.05). CONCLUSION: CDD in combination with drospirenone and ethinylestradiol tablets (II) may be effective in treating PCOS by improving obesity, glucose metabolism and lipid metabolism with no serious adverse events, making it a feasible clinical practice option.

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

CONTEXT: Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE: To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS: This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS: The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION: To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

A Review of Levodopa Formulations for the Treatment of Parkinson's Disease Available in the United States.

Purpose: The safety and efficacy of levodopa formulations are evaluated to inform clinical decision making for the treatment of Parkinson's disease. Summary: Levodopa is a cornerstone of treatment for Parkinson's disease due to its proven efficacy. Although many patients can initially be managed using immediate release tablets, as their disease progresses they often require escalating doses as well as more frequent dosing to prevent wearing off effects. Additionally, patients who experience time in the off state may struggle with the delay between medication administration and onset of action. Therefore, to increase patient convenience as well as to enhance the pharmacokinetic profile of the levodopa, several other formulations have been developed. Levodopa coformulated with carbidopa is supplied as immediate release tablets, oral disintegrating tablets, controlled release tablets, extended release capsules, and a continuous enteral solution. Additionally, there is a levodopa inhalation powder available. As a result of their different absorption profiles, each formulation has unique safety and efficacy attributes. Consequently, while this expansion of levodopa formulations has substantially increased treatment options for patients, it has also increased the complexity of medical decision making for patients, providers, and health systems alike. Conclusion: Knowledge of the different pharmacokinetic, safety and efficacy profiles of the available levodopa formulations is critical for the effective management of Parkinson's disease on both the individual patient and population levels.

Insight of the Biopharmaceutical Implication of Sleeve Gastrectomy on Levothyroxine Absorption in Hypothyroidism Patients.

PURPOSE: The growing rate of obesity led to an increased number of bariatric surgeries (BS) as a treatment option for obesity. The gastrointestinal tract (GIT) changes following BS can impact many drugs' absorption. Levothyroxine (LT4) is a synthetic thyroxine (T4) replacement used commonly as tablets to manage hypothyroidism disorder, which is more prevalent among patients with obesity. This study aims to examine the LT4 oral tablet form therapy after sleeve gastrectomy. MATERIALS AND METHODS: A retrospective cohort study was conducted in multi-center. The LT4 doses and TSH and T4 levels were compared before and after BS. The post-surgery readings were categorized into three periods: (one to three months), (four to six months), and (> six ) months after surgery. ANOVA test was used for analysis. RESULTS: A total of 14374 patients who underwent BS from (1/2019 to 3/2022) were screened for eligibility, and n = 101 participants matched the inclusion criteria. The TSH and T4 were not statistically significant differences before and after surgery (P-values of 0.4864 and 0.5970, respectively). However, the doses significantly differed before and after surgery in all the follow-up time point periods (P < 0.002). CONCLUSION: The LT4 required doses significantly reduced after sleeve gastrectomy, which can be related to the improved endogenous thyroid production in patients with obesity. However, the abnormality of the GIT induced by the sleeve gastrectomy may affect the exogenous LT4 absorption. Using liquid forms of LT4 while monitoring the thyroid function parameters can optimize the treatment after the procedure.

No drug-drug interactions between selective prolyl-tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants.

Bersiporocin, a potent and selective prolyl-tRNA synthetase inhibitor, is expected to show a synergistic effect with pirfenidone or nintedanib in patients with idiopathic pulmonary fibrosis. To validate the combination therapy of bersiporocin with pirfenidone or nintedanib, a randomized, open-label, two-part, one-sequence, three-period, three-treatment study was designed to evaluate the effect of drug-drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric-coated bersiporocin tablet were evaluated after single and multiple administrations. The potential effects of cytochrome P450 2D6 (CYP2D6) genotyping on bersiporocin pharmacokinetics and DDI were also explored. In Part 1, participants were sequentially administered a single dose of pirfenidone 600 mg, a single dose of bersiporocin 150 mg followed by multiple doses, and bersiporocin in combination with pirfenidone. In Part 2, participants were sequentially administered a single dose of nintedanib 150 mg, multiple doses of bersiporocin 150 mg, and bersiporocin in combination with nintedanib. Forty-six participants completed the study. There was no significant pharmacokinetic DDI between bersiporocin, and pirfenidone or nintedanib. All adverse events (AEs) were mild to moderate and did not include serious AEs, suggesting bersiporocin alone or in combination therapy were well-tolerated. The newly formulated bersiporocin 150 mg tablet showed a moderate accumulation index. There was no significant difference in the pharmacokinetic profiles after administration of bersiporocin alone or in combination therapy between CYP2D6 phenotypes. In conclusion, there are no significant DDI regarding the pharmacokinetics, safety, and tolerability of bersiporocin administration with pirfenidone or nintedanib.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.