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Some medications are unsuitable for one-dose packaging due to issues such as moisture absorption. A survey of community pharmacists was conducted to understand the status of one-dose packaging and identify hygroscopic medications for stability testing. Stability was assessed using a moisture-suppression bag and clinical applications were investigated. Survey results were used to extract the medications that should be included in the one-dose package. Medications were stored with and without moisture-suppression bags, and quality was assessed using weight change and breaking force. Suvorexant, Telmisartan, Aspirin Dialuminate, Kampo extract formulations (Yokukansan and Daikenchu-tou), and Yokuinin extract tablets were selected for the stability test. Storage without moisture-suppression bags resulted in substantial changes in weight and breaking force for all tested medications; the use of moisture-suppression bags maintained the quality of some medications. Although there was a substantial difference in weight change from day 3, there was almost no change in appearance. Currently, the decision to include hygroscopic pharmaceuticals in a single package based on changes in appearance is insufficient. However, further research is necessary to justify the decision not to include hygroscopic pharmaceuticals in such packaging. Therefore, pharmaceutical companies should cultivate appropriate awareness and information literacy of pharmacists should be improved. [ABSTRACT FROM AUTHOR]

The presented work aimed to investigate the effect of thermal treatment on sludge from wastewater treatment plants (WWTPs) in the Slovak Republic on the content of pharmaceuticals (PhACs) and illicit drugs. Sludge samples from eight WWTPs (total flows of 6900–62,500 m3/day, number of population equivalents over 40,000 for each WWTP, production of sludge 400–3300 tons DM/year) were treated with thermal processes in the temperature range of 80 to 550 °C. More than 100 compounds were studied in the sludge samples, but in this article, we deeply focused on the fate of the thirteen most concentrated and frequently found PhACs (azithromycin, carbamazepine, cetirizine, citalopram and its metabolite N-desmethylcitalopram, diclofenac, fexofenadine, sertraline and its metabolite norsertraline, telmisartan, trazodone, valsartan, and verapamil). The thermal processes used showed a decrease in PhAC concentrations already at 80 °C when the total concentration of selected PhACs decreased to 81%. In thermally treated sludge samples at 250 °C, only telmisartan at all studied WWTPs and diclofenac at WWTP Banská Bystrica stayed above the limits of quantification (LOQs), while the temperature of 550 °C led to a decrease in all thirteen PhACs below LOQs. [ABSTRACT FROM AUTHOR]

Background and Objective: Telmisartan exhibits significant pharmacokinetic (PK) variability, but it remains unclear whether its PK profile is altered in hypertensive patients. This study aimed to characterize telmisartan PKs by conducting a meta-analysis and developing a pooled population PK model based on data from healthy subjects and hypertensive patients. Methods: Relevant literature was identified by a systematic approach. Eighteen studies were selected for analysis, which included 394 healthy subjects receiving single doses of telmisartan, 190 healthy subjects receiving repeated doses, along with 295 hypertensive patients receiving repeated doses. Pooled population PK analysis incorporated 20 mean concentration-time profiles from 14 studies. Meta-analyses were performed using OpenMeta-Analyst, and population PK modeling was performed using NONMEM®. Results: Repeated telmisartan doses increased peak plasma concentrations. However, other noncompartmental PK parameters remained consistent across healthy and hypertensive populations. Telmisartan PKs were best described using a two-compartment model with first-order absorption and elimination in pooled analysis. Typical PK parameter values for apparent clearance (CL/F), apparent central and peripheral volumes of distribution (V1/F and V2/F), absorption rate constant (ka), and absorption lag time were 18.3 L/h, 20.7 L, 360 L, 0.183 h−1 and 0.228 h, respectively. Interindividual variabilities in CL/F, V1/F, and ka were 84%, 122%, and 106%, respectively. Covariate analysis revealed significantly lower CL/F (63.7%) and V1/F (90.3%) values in hypertensive patients than healthy subjects. Conclusion: These findings quantified the variability of telmisartan PK profile and highlighted the differences between healthy individuals and hypertensive patients, suggesting the need for optimized dosage strategies to improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Censoring at death is the only feasible option if death is not recorded and individuals who died simply no longer contribute visits, such as in the setting of Barberio et al (Am J Epidemiol. 2024;193(9):1281-1290) before they acquired access to mortality information. Censoring at death is known to lead to biased estimates of the probability of the event of interest before time |$t$|⁠. Barberio et al showed through simulations that this bias increases with increasing mortality. However, when analyzing claims data it is often important to not exclude individuals with shorter life expectancies: An important strength of observational studies is that they allow estimation of treatment effects in more varied populations than are typically included in randomized clinical trials. In this commentary, I derive an analytical expression for the bias and provide 2 upper bounds for the bias. The bounds inform the usefulness of obtaining mortality information. If the probability of death before the event is known to be small, wider CIs can be created using the first bound on the bias; an algorithm is provided. If the bias is large, obtaining mortality information is important. Barberio et al show that obtaining mortality information can be essential in practice. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Telmisartan is an angiotensin receptor blocker (ARB) approved by the Food and Drug Administration of the US for the treatment of hypertension. It possesses unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a 24-h sustained reduction of blood pressure. Besides well-known antihypertensive and cardioprotective effects, there is also strong clinical evidence that telmisartan confers renoprotection. Aryl hydrocarbon receptor (AhR) belongs to the steroid receptor family. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous ligand of AhR. Cytochrome P450 (CYP) 1A1 is an AhR-target gene. In this article, we demonstrated that telmisartan (2.5–60 μM) enhanced CYP1A1 promoter activity and expressions of mRNA and protein. Telmisartan-induced CYP1A1 expression was blocked by the AhR antagonist CH-223191 in liver cell lines and was negligible in the AhR signaling-deficient mutant cells. In addition, telmisartan induced transcriptional activity mediated by aryl hydrocarbon response element in both human and mouse cells, and was able to induce AhR translocation into the nucleus. Accordingly, telmisartan is an AhR agonist. It also acted synergistically with ITE to further enhance the expression of CYP1A1 mRNA and protein. This synergistic effect was more pronounced in cells with AhR overexpression compared to those without. AhR activity has strong association with the progression of chronic renal disease. Our study demonstrated that telmisartan is an AhR agonist and has synergistic effect with ITE, an indole derivative, to potentiate the effect on AhR. This finding may provide additional clues about the mechanism of the protective effect of telmisartan on the kidney. [ABSTRACT FROM AUTHOR]

For compendial dissolution testing of solid dosage forms, media volumes of 500 to 900 mL are used in apparatus I and II to ensure sink conditions. However, these volumes are considerably larger than those in the gastrointestinal tract. Thus, the experiments are not biomimetic and possibly not suitable for biopredictive dissolution testing. The present study investigates the influence of volumes of dissolution media in non-compendial dissolution/permeation settings. Dissolution/permeation studies of two commercial bilayer tablets (Twynsta® and Arrow) containing the active pharmaceutical ingredients telmisartan (40 mg) and amlodipine (10 mg) were evaluated using the MacroFlux tool with various biomimetic media mimicking fasted and fed states as well as biological variability ("biorelevant"). Particularly, the two-stage dissolution process of telmisartan from the tablets is interesting because the compound has a pH-dependent solubility, and 2-stage dissolution leads to supersaturation and precipitation upon pH shift. For telmisartan, lower dissolution volumes significantly induced precipitation, leading to lower permeation, while no precipitation was observed in the larger volume. The permeation of telmisartan was overly sensitive to both pH and micelle concentrations in the biomimetic media. Amlodipine showed complete dissolution under any conditions, which correlates with its known complete absorption in vivo. In conclusion, volumes of dissolution media (and their compositions) are key parameters and play a significant role for designing relevant biomimetic experiments used to predict the bioavailability of supersaturating systems. [Display omitted] [ABSTRACT FROM AUTHOR]

The detection and quantification of genotoxic impurities, specifically nitrosamines, in pharmaceuticals have garnered high regulatory attention due to their potential carcinogenic effects. This study presents a comprehensive validation of a liquid chromatography with Atmospheric Pressure Chemical Ionization (APCI) Coupled with Triple Quardrapole Analyser (LC-MS/MS) method tailored for the determination of multiple nitrosamine impurities including N-nitrosodimethylamine (NDMA), N-nitroso methyl butyl amine (NMBA), N-nitrosodiethylamine (NDEA), N-nitroso diethyl isopropyl amine (NEIPA), N-nitrosodiisopropylamine (NDIPA), N-nitroso methyl ethyl amine (NMPA), N-nitroso propyl amine (NDPA), N-nitrosopiperidine (NPIP), N-nitrosopyrrolidine (NPYR), and N-nitroso butyl amine (NDBA) in telmisartan tablet formulations. The method was meticulously validated according to the International Council for Harmonisation (ICH) guidelines, focusing on critical parameters such as specificity, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), and filter compatibility. The specificity of the method was rigorously established, demonstrating unequivocal differentiation between nitrosamine impurities and potential interferences from excipients and active pharmaceutical ingredients (APIs). Recovery studies validated the method's accuracy, yielding recoveries within the acceptable range of 70–120% across various concentration levels, confirming its reliability for routine analysis. Precision was assessed through the relative standard deviation (RSD) of multiple replicate analyses, with RSD values consistently below the ICH threshold of < 15%, underscoring the method's reproducibility. Sensitivity assessments revealed exceptional LODs as low as 10.76 ppb and LOQs around 33.00 ppb for several nitrosamines, significantly exceeding current regulatory limits for genotoxic impurities. Evaluations of filter compatibility indicated that both 0.22 µm PVDF and 0.2 µm nylon filters are effective for sample preparation, ensuring the integrity of the analytes during the filtration process. Upon application of the validated method to commercial 40 mg telmisartan tablets, all targeted nitrosamines were undetected, affirming the method's applicability in routine quality control settings. This work culminates in the establishment of a highly sensitive, specific, and robust LC–MS/MS methodology for the detection of nitrosamine impurities in telmisartan, addressing regulatory concerns while ensuring patient safety. The low detection thresholds provided by this method position it as an invaluable tool for pharmaceutical manufacturers and regulatory bodies, facilitating stringent monitoring and compliance with safety standards, ultimately enhancing the safety profile of medicinal products in the market. [ABSTRACT FROM AUTHOR]

Background: Telmisartan and bisoprolol fumarate together are two medications that diminish arterial pressure. The current study comprises an evaluation of the proposed methodology's greenness regarding the HPLC method used to govern the medication mixture regardless of dose form A novel stability suggesting HPLC method's environmental effect was evaluated using the greenness metrics. Stress conditions comprising acidic, alkaline, oxidative, thermal, and photolytic degradation were applied for both of the medications. Results: The RP—HPLC method employing a reversed-phase C18 column with a gradient approach, the HPLC chromatography was carried out. The mobile phase consisted of acetonitrile, methanol, and phosphate buffer (60:35:5, %v/v/v), with the stationary phase being the Unisphere C18 column Agela Tech. The RP-HPLC method uses UV detection at 224 nm with chromatographic purification spanning linearities of 2.5–12.5 μg/mL for bisoprolol fumarate and 40.0–200.0 μg/mL for telmisartan, correspondingly. The procedure is accurate and precise, as demonstrated by an outcome that % RSD inside the permissible range. Additionally, various stressors were introduced to the medications. The approach's green credentials with respect to solvent utilization, chemical substances, expenditure of energy, and waste formation have been verified by the greenness data collected during the evaluation. No chromatographic or spectrum impediments caused by formulation additives have been observed. Conclusion: Bisoprolol fumarate and telmisartan could be measured simultaneously using the devised RP-HPLC method, which was simple, quick, sensitive, accurate, precise, linear, and stability indicating. The proposed approach showed ecological friendliness, robustness, sensitivity, and ease of use. As a result, the devised method could be applied to the regular quality checking of tablets and bulk medications. [ABSTRACT FROM AUTHOR]

The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension and dyslipidemia are common contributors to cardiovascular disease (CVD), often occurring together. Effectively Managing both is key to reducing mortality and morbidity, but complex regimens reduce adherence. Aim: This study investigated the comparative efficacy and safety of a three-drug regimen (TAR) containing telmisartan, amlodipine, and rosuvastatin against two-drug combinations (TA and TR) for managing hypertension and dyslipidemia. Methods: We searched PubMed, Web of Science, Cochrane, Embase, and Scopus databases for relevant articles matching our inclusion criteria. Following the application of inclusion criteria, four studies were selected for qualitative analysis and four studies for meta-analysis. Results: Our analysis showed TAR [n = 155] significantly reduced mean systolic blood pressure (MSSBP) at week 4 compared to TR (n = 163) (MD = -15.65 mmHg) and TA (MD = -4.63 mmHg). TAR also showed superiority over all groups (TR [n = 163], TA [n = 162]) in MSSBP reduction. For low-density lipoprotein-cholesterol (LDL-C), TAR only showed a significant difference at week 4 compared to TA (MD = -86.41 mg/dL), with no difference between TAR and TR at either week 4 or 8. Conclusion: Our findings suggest that TAR may be a safe and effective therapeutic option for the concurrent management of hypertension and dyslipidemia. However, there is no significant difference regarding adverse events between both arms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Effects of the renin-angiotensin-aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. OBJECTIVES: To characterize the RAAS in untreated dogs with pCKD compared to healthy, life-stage- and sex-matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. ANIMALS: Dogs with pCKD (n = 36) and healthy controls (n = 20). METHODS: Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7, and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. RESULTS: Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1-5, and 1-7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan- and enalapril-treated pCKD dogs, respectively (both P

Tefluthrin (Tef) is categorized as a type-I pyrethroid insecticide, telmisartan (Tel) functions as an angiotensin II receptor blocker, and KB-R7943 has been identified as an inhibitor of the Na+-Ca2+ exchange process. However, the influence of these compounds on the amplitude and gating properties of voltage-gated Na+ current (INa) in neurons associated with pain signaling remains unclear. In cultured dorsal root ganglion (DRG) neurons, whole-cell current recordings revealed that Tef or Tel increased the peak amplitude of INa, concomitant with an elevation in the time constant of INa inactivation, particularly in the slow component. Conversely, exposure to KB-R7943 resulted in a depression in INa, coupled with a decrease in the slow component of the inactivation time constant of INa. Theoretical simulations and bifurcation analyses were performed on a modeled interneuron in the spinal dorsal horn. The occurrence of INa inactivation accentuated the subthreshold oscillations (SO) in the membrane potential. With an increase in applied current, SO became more pronounced, accompanied by the emergence of high-frequency spiking (HS) with a frequency of approximately 150 Hz. Moreover, an elevation in INa conductance further intensified both SO and HF. Consequently, through experimental and in silico studies, this work reflects that Tef, Tel, or KB-R7943 significantly impacts the magnitude and gating properties of INa in neurons associated with pain signaling. The alterations in INa magnitude and gating in these neurons suggest a close relationship with pain transmission.

Abstract Hypertension is a chronic condition with multiple drug regimens. Limiting these medicines is critical to patient compliance. Therefore, bisoprolol and telmisartan were recently developed in a fixed-dose combination to control blood pressure. The UV absorption spectra of bisoprolol and telmisartan overlapped significantly. Thus, three spectrophotometric methods have been developed for simultaneous determination of bisoprolol and telmisartan without prior separation. Method A is ratio difference of ratio spectra (RD), which measures the amplitude difference between (210–224) nm for bisoprolol and between (255–365) nm for telmisartan. Method B, the first derivative of ratio spectra (1DD), measures amplitude signals at 232 and 243 nm for bisoprolol and telmisartan, respectively. Method C is the mean centering of ratio spectra (MC), which measures the mean-centered ratio spectra's values at 223 nm for bisoprolol and 245 nm for telmisartan. The applied methods showed good linearity 2–20 µg/mL for bisoprolol, 4–32 µg/mL for telmisartan, with sufficient accuracy and precision. The methods were sensitive, with LOD values of 0.243 µg/mL and 0.596 µg/mL in RD method, 0.313 µg/mL and 0.914 µg/mL in 1DD method, and 0.406 and 0.707 µg/mL in MC method for bisoprolol and telmisartan, respectively, the methods were validated per ICH criteria. The novel methods are precise and accurate and can be used for routine analysis and quality control of bisoprolol and telmisartan in pure and dosage form. Furthermore, the greenness of the approaches was evaluated using Analytical Greenness assessment (AGREE), and the suggested method received a high greenness score.

Abstract Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein

Single-pill combinations of 3 or more low-dose blood pressure (BP)–lowering drugs hold promise for initial or early treatment of hypertension. The authors conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety. This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event. From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were −7.3 mm Hg (95% CI: −4.5 to −10.2) for GMRx2 ¼ dose and −8.2 mm Hg (95% CI: −5.2 to −11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group. In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306) [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigates the impact of supercritical antisolvent (SAS) process parameters on the particle formation of telmisartan, a poorly water-soluble drug. Methods: A fractional factorial design was employed to examine the influence of the SAS process parameters, including solvent ratio, drug solution concentration, temperature, pressure, injection rate of drug solution, and CO₂ flow rate, on particle formation. Solid-state characterizations of the SAS process particles using XRD and FT-IR confirmed their amorphous nature. The effect of particle size on the kinetic solubility, dissolution, and oral bioavailability of telmisartan was also assessed. Results: Using a mixture of dichloromethane and methanol, telmisartan amorphous nano-microparticles with sizes between 200 and 2000 nm were produced. The key parameters, particularly drug solution concentration and temperature, significantly affected the particle size. Interestingly, the ratio of the solvent mixture also had a significant effect on the particle morphology. Further experiments were performed to determine the conditions for preparing telmisartan amorphous nano-microparticles with various sizes by controlling the solvent mixture ratio and the concentration of the drug solution. It was revealed that a reduction in the amorphous particle size enhanced both the kinetic solubility and dissolution rates, leading to a significantly increased in vivo oral bioavailability in rats compared to unprocessed telmisartan. Conclusions: These findings suggest that SAS processing, utilizing adjustments of process parameters, offers an effective strategy for enhancing the bioavailability of poorly soluble drugs by generating amorphous spherical nano-microparticles with optimized particle size. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial), each prevent cardiovascular disease. However, trial results may not be generalizable, and their effectiveness in underrepresented groups is unclear. Using trial emulation methods within routine-care data to validate findings, we explored the generalizability of ONTARGET results. For people prescribed an ACEi/ARB in the UK Clinical Practice Research Datalink GOLD dataset from January 1, 2001, to July 31, 2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB with ACEi, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure) and secondary outcomes. Because the prespecified criteria were met, confirming trial emulation, we then explored treatment heterogeneity among 3 trial-underrepresented subgroups: females, persons aged ≥75 years, and those with chronic kidney disease. In the trial-eligible population (n  = 137 155), results for the primary outcome demonstrated similar effects of ARB and ACEi (hazard ratio = 0.97; 95% CI, 0.93-1.01), meeting the prespecified validation criteria. When extending this outcome to trial-underrepresented groups, similar treatment effects were observed by sex, age, and chronic kidney disease. This suggests that ONTARGET trial findings are generalizable to trial-underrepresented subgroups. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

ABO group incompatibility at the time of transfusion of blood products carries risks ranging from mild adverse reactions to death of the patient. In modern obstetrics, the leading cause of death is obstetric hemorrhage, for which uterotonics, compression sutures, arterial ligatures, solutions, and blood products are used. For this reason, it is necessary to know the blood group . and Rh of each patient admitted for obstetric surgery and have her sign a consent form for transfusion of blood or blood derivatives, explaining all the adverse effects that may occur in the event of complications. We describe a case of postpartum transfusion with a hemolytic reaction due to ABO incompatibility and its clinical management. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach. Methods: Seven weeks after initiating a high-fat diet (HFD), C57BL/6N mice received fecal microbiota for 8 weeks from donor mice by oral gavage, continuing HFD feeding. Stool samples came from mice that were treated with TEL (8 mg/kg/d by gavage, 12 weeks), thus remaining lean despite HFD feeding (BL/6>fTEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>fVEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing. Results: Weight gain was lower in BL6>fTEL than in BL6>fVEH mice after 3 but not 8 weeks. Energy homeostasis, insulin sensitivity, and body composition did not differ between the two groups. β-diversity indicated group differences (F = 2.27, p = 0.005). Although the Firmicutes/Bacteroides ratio did not differ, abundances of distinct phyla, families, and genera varied. Among others, Ruminococcaceae and Desulfovibrionaceae, Desulfovibrionia uncl., and Lachnospiraceae uncl. were lower in BL/6>fTEL than in BL/6>fVEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>fVEH and negative in BL/6>fTEL mice. Discussion: As FMT from TEL-pretreated mice influences the microbiota in acceptor mice with slight weight-reducing effects, we confirm the relevance of TEL-related microbiota changes for weight reduction, most likely independent of the transferred stool-residual TEL effect on the host metabolism. [ABSTRACT FROM AUTHOR]

Tefluthrin (Tef) is categorized as a type-I pyrethroid insecticide, telmisartan (Tel) functions as an angiotensin II receptor blocker, and KB-R7943 has been identified as an inhibitor of the Na+-Ca2+ exchange process. However, the influence of these compounds on the amplitude and gating properties of voltage-gated Na+ current (INa) in neurons associated with pain signaling remains unclear. In cultured dorsal root ganglion (DRG) neurons, whole-cell current recordings revealed that Tef or Tel increased the peak amplitude of INa, concomitant with an elevation in the time constant of INa inactivation, particularly in the slow component. Conversely, exposure to KB-R7943 resulted in a depression in INa, coupled with a decrease in the slow component of the inactivation time constant of INa. Theoretical simulations and bifurcation analyses were performed on a modeled interneuron in the spinal dorsal horn. The occurrence of INa inactivation accentuated the subthreshold oscillations (SO) in the membrane potential. With an increase in applied current, SO became more pronounced, accompanied by the emergence of high-frequency spiking (HS) with a frequency of approximately 150 Hz. Moreover, an elevation in INa conductance further intensified both SO and HF. Consequently, through experimental and in silico studies, this work reflects that Tef, Tel, or KB-R7943 significantly impacts the magnitude and gating properties of INa in neurons associated with pain signaling. The alterations in INa magnitude and gating in these neurons suggest a close relationship with pain transmission. [ABSTRACT FROM AUTHOR]

Background: Telmisartan's low solubility limits its bioavailability, leading to poor dissolution, reduced efficacy, and decreased patient compliance. This study assesses the dissolution and quality control of various commercially available 40 mg telmisartan IP tablets, all marketed as bioequivalent. Methods: The study analyzed various marketed formulations containing Telmisartan. Both the marketed products and Tazloc were evaluated through dissolution studies (drug release), with drug quantification performed using ultraviolet visible spectroscopy (Jasco UV-730) at max values of 291 nm and 296 nm. Results: Tazloc demonstrated a drug release of 65% in 60 minutes in pH 1.2 HCl, outperforming other commercial tablets. In comparison, Brand A, Brand B, and Brand C each showed less than 60% release within the same period. Additionally, Tazloc exhibited the highest release--over 10% more than the other brands--in pH 4.5. In vitro release studies in pH 6.8 revealed that Tazloc achieved 95% release in 60 minutes, while Brand A, Brand B, and Brand C reached 91%, 82%, and 62%, respectively. Similarly, in pH 7.5 phosphate buffer, the cumulative drug release after 60 minutes was 99% for Tazloc, followed by 96% for Brand A, 94% for Brand B, and 93% for Brand C. Conclusion: Tazloc, utilising ODCA technology, exhibits superior dissolution and solubility compared to conventional brands, ensuring enhanced bioavailability and optimal blood pressure control, leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Aging and age-related diseases, which include the most relevant chronic non-infectious diseases (arterial hypertension, coronary heart disease, type 2 diabetes mellitus), are attributed to the accumulation of advanced glycation end-products (AGEs) in various organs and tissues. Glycation (non-enzymatic glycosylation) is the name given to the in vivo reaction of reducing carbohydrates and free amino groups of proteins, lipids, and nucleic acids. It has many negative biological effects mediated by disruption of the conformation of structural proteins, enzymes, and nucleic acids at the intracellular level and in the extracellular matrix. The consequences of AGE accumulation are difficult to reverse because of the long half-life and slow elimination of AGEs, which makes the development of technologies aimed at blocking the reactions leading to their formation an urgent and important goal. Currently, pharmacology is faced with the task of searching for molecules with promising antiglycating properties. Identification of drugs that prevent glycation among well-known drugs in clinical practice is a necessary step in solving this problem. The antiglycation properties of such drugs (metformin, ramipril, telmisartan, etc.) are discussed in this review as a little-known component of their pleiotropy. The drugs are classified according to the mechanism of their antiglycation effect. [ABSTRACT FROM AUTHOR]

Background Class-I residual solvents such as 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, 1,2-dichloroethane are toxic, environmental hazards, and carcinogenic to humans. A headspace-gas chromatography–mass spectrometer is a sophisticated instrument for the quantification of residual solvents at lower limits. Objective An exact, sensitive, reliable, and fast method was developed to determine 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, and 1,2-dichloroethane present in different drug substances using a headspace-gas chromatography–mass spectrometer. Methods Helium is used as a carrier gas. N-methyl-2-pyrrolidone is used as a diluent, and the stationary phase is a DB-624 (60 m × 0.25 mm × 1.4 μm film thickness) column with a flow rate of 1.5 mL/min. Results The concentration LODs for 1,1-dichloroethene, 1,1,1-trichloroethane, carbon tetrachloride, benzene, and 1,2-dichloroethane were 0.24, 5, 0.12, 0.06, and 0.15 ppm. The concentrations LOQs for the aforementioned impurities were 0.8, 15, 0.4, 0.2, and 0.5 ppm. The linearity was assessed over the range from LOQ to 120% of the specification level. Conclusion The current method's system suitability, precision, linearity, and accuracy parameters were assessed in accordance with the United states pharmacopeia (USP) < 1225> and International Conference on Harmonization of technical standards for the registration of medicines for human use (ICH) Q2(R2), and the results were within the acceptance criteria. Highlights No research studies have been reported on determining class-I residual solvents in lincomycin hydrochloride, dapagliflozin, vonoprazan fumarate, and telmisartan drug substances. The proposed research aims to develop a common method for the quantification of class-I residual solvents for drug substances. The quality by design (QbD) concept is utilized in performance verification. [ABSTRACT FROM AUTHOR]