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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

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]

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]

Precise, accurate, and sensitive high performance thin layer chromatographic method has been developed and validated for simultaneous determination of efonidipine hydrochloride (EFD) and telmisartan (TEL) in a tablet dosage form which is used in treatment of hypertension. The proposed method used aluminum plates pre-coated with silica gel 60 F254 as a stationary phase and n-butanol: toluene: acetic acid (3:7:0.2, v/v/v) as a mobile phase for separation purpose. Compact spots of TEL and EFD were obtained at Rf 0.73 and 0.37, respectively. Densitometric detection was carried out at 299 nm in UV. Linear responses were shown by the detector over the range of 200–1200 ng/band for both drugs. The proposed method was validated as per ICH guidelines. The method was successfully applied for estimation of both drugs in tablet formulations. Forced degradation study was carried and efonidipine was found to be susceptible to base hydrolysis and oxidative stress degradation while TEL was stable in acid-base hydrolysis, oxidative stress, dry heat and photo stability testing conditions. The developed method can be used for the analysis of stability samples. Greenness assessment of developed method was performed using AGREE software. The method was found to be greener having greenness score of 0.69. [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]

Background: Alzheimer's disease (AD) is regarded as one of the most common neurodegenerative diseases. It is a chronic, slowly progressing neurological illness that inhibits memory, cognition, and behavior. This research aimed to evaluate the protective effect of angiotensin II type I receptor (AT1R) blockers versus vitamin B12 (VB12) on the AD rat model. Methods: Thirty adult local strain male albino rats were randomly subdivided into 5 equal groups: Group I (control): vehicle only. Group II (AlCl3 induced AD group): AlCl3 175 mg/kg orally. Group III: telmisartan + AlCl3, Group IV: vitamin B12 + AlCl3, and Group V: vitamin B12 + telmisartan + AlCl3. Modified T maze test was used to evaluate the animal behavior. Rotarod test was employed to assess the animal muscle strength. In addition, serum and hippocampal level of brain derived neurotropic factor (BDNF) were assessed. Also, serum level of MDA and SOD were measured. Additionally, histopathological examination of hippocampus and brain tissue was performed. Results: AlCl3 administration resulted in changes similar to AD as proved by deterioration in behavioral tests, significant reduction in serum and hippocampal BDNF, serum SOD and significant increase in serum MDA level along with corresponding histopathological changes in hippocampus. Furthermore, vitamin B12 and telmisartan ameliorated the previously measured chemical biomarkers and behavioral parameters. Also, the antioxidant power was enhanced with combination prophylaxis therapy of both vitamin B12 and telmisartan. Conclusion: Angiotens in type 1 receptor blockade by telmisartan and vitamin B12 administration each one alone or both in combination could have a potential prophylactic and/or therapeutic effect in AD. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: The antihypertensive effects of angiotensin II receptor blockers (ARBs) are well recognized. However, conventional meta-analyses have reported inconsistent results on their efficacy and safety. Aim: This study aimed to evaluate the efficacy and safety of six ARBs (losartan, valsartan, irbesartan, telmisartan, candesartan, and olmesartan) commonly used to treat hypertension, using a network meta-analysis. Method: We retrieved randomized controlled trials on hypertension treatment using ARBs from the PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases. The efficacy outcomes included absolute changes in office systolic and diastolic blood pressure from baseline, and 24-h ambulatory blood pressure. Safety outcomes were assessed by the total number of adverse events (AEs) during treatment. We conducted the network meta-analysis using the 'bugsnet' and 'gemtc' packages in R. Results: A total of 193 studies were included. Olmesartan had the highest surface under the cumulative ranking in reducing office systolic (91.4%) and diastolic blood pressure (87.2%). Candesartan has the highest ranking in lowering 24 h ambulatory systolic blood pressure (95.4%), while telmisartan reduced 24 h ambulatory diastolic blood pressure (83.4%). Olmesartan also ranked highest in safety (70.8%). Conclusion: Valsartan and losartan were less effective in lowering blood pressure than other drugs, with no significant differences. Olmesartan and telmisartan were associated with fewer AEs than losartan, although the incidence of adverse events was similar between the other blockers. Olmesartan and telmisartan demonstrated the best balance of antihypertensive efficacy and minimal adverse events. More research is needed to confirm whether telmisartan and olmesartan are optimal choices for controlling blood pressure in patients. [ABSTRACT FROM AUTHOR]

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

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 Cardiovascular diseases, especially hypertension, stand as prominent contributors to global mortality. Hypertension, often referred to as a silent killer syndrome, necessitates the use of multiple medications for effective control and management. A new environmentally friendly HPLC–DAD method is introduced in this study for the concurrent analysis of telmisartan (TEL), chlorthalidone (CHT) and amlodipine besylate (AML), in both pure forms and combined pharmaceutical dosage form. An isocratic elution mode was employed to achieve chromatographic separation, utilizing an Inertsil C18 column (250 × 4.6 mm, 5.0 µm) and a mobile phase mixture of acetonitrile and phosphate buffer (pH 3.0 ± 0.1) with ratio of 35:65, v/v. The separation was achieved within 10 min at a flow rate of 1.0 mL/min. The proposed method's validation was carried out following the guidelines outlined by the International Council for Harmonisation (ICH). The achieved linearity range was 1.0–140.0 μg/mL for TEL and 1.0–100.0 μg/mL for CHT and AML with quantification limits of 0.061, 0.177, and 0.313 μg/mL for TEL, CHT, and AML, respectively. The fixed combination tablet dosage form demonstrated acceptable release profile, as indicated by the in-vitro dissolution studies. The studied dissolution media were phosphate buffer pH 7.5, 0.01 N HCl, and water, utilizing a USP type II apparatus at 37 ± 0.5 °C with a stirring rate of 75 rpm. The proposed method was applied successfully for the quality assessment of Telma-ACT® Tablets with good precision and accuracy. Various tools were used for evaluating the level of greenness, including Green Analytical Procedure Index (GAPI), Analytical Greenness Metric for Sample Preparation (AGREEprep), Analytical Eco-Scale (AES), and Analytical Method Greenness Score (AMGS). These tools had confirmed the eco-friendliness of the proposed method. Additionally, the newly introduced White Analytical Chemistry (WAC), and the Blue Applicability Grade Index (BAGI) have been specifically developed to evaluate the sustainability and the applicability of the method.

Abstract Background Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions.

Hyunwook Ryu,1 Hyun Chul Kim,1 Inseung Jeon,1 In-Jin Jang,1 Joo-Youn Cho,1,2 Kyung Tae Kim,3 Jaeseong Oh1,4,5 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Addpharma, Inc., Yongin-si, Gyeonggi-do, Republic of Korea; 4Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of Korea; 5Clinical Research Institute, Jeju National University Hospital, Jeju, Republic of KoreaCorrespondence: Jaeseong Oh, Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of Korea, Email jaeseong5@jejunu.ac.krBackground: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA).Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study.Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (μg/L) and the area under the plasma concentration-time curve (h·μg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765– 1.2017) and 0.9359 (0.7847– 1.1163); free ezetimibe, 1.5713 (1.2821– 1.9257) and 0.9941 (0.8384– 1.1788); rosuvastatin, 2.1673 (1.7807– 2.6379) and 1.1714 (0.9992– 1.3733); telmisartan, 1.0745 (0.8139– 1.4186) and 1.1057 (0.8379– 1.4591); and amlodipine, 0.9421 (0.8764– 1.0126) and 0.9603 (0.8862– 1.0405). Both combination therapy and monotherapy were well tolerated by the subjects.Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.Keywords: drug‒drug interactions, pharmacokinetics, fixed-dose combination, ezetimibe, rosuvastatin, telmisartan, amlodipine

Cardiovascular diseases, especially hypertension, stand as prominent contributors to global mortality. Hypertension, often referred to as a silent killer syndrome, necessitates the use of multiple medications for effective control and management. A new environmentally friendly HPLC–DAD method is introduced in this study for the concurrent analysis of telmisartan (TEL), chlorthalidone (CHT) and amlodipine besylate (AML), in both pure forms and combined pharmaceutical dosage form. An isocratic elution mode was employed to achieve chromatographic separation, utilizing an Inertsil C18 column (250 × 4.6 mm, 5.0 µm) and a mobile phase mixture of acetonitrile and phosphate buffer (pH 3.0 ± 0.1) with ratio of 35:65, v/v. The separation was achieved within 10 min at a flow rate of 1.0 mL/min. The proposed method's validation was carried out following the guidelines outlined by the International Council for Harmonisation (ICH). The achieved linearity range was 1.0–140.0 μg/mL for TEL and 1.0–100.0 μg/mL for CHT and AML with quantification limits of 0.061, 0.177, and 0.313 μg/mL for TEL, CHT, and AML, respectively. The fixed combination tablet dosage form demonstrated acceptable release profile, as indicated by the in-vitro dissolution studies. The studied dissolution media were phosphate buffer pH 7.5, 0.01 N HCl, and water, utilizing a USP type II apparatus at 37 ± 0.5 °C with a stirring rate of 75 rpm. The proposed method was applied successfully for the quality assessment of Telma-ACT® Tablets with good precision and accuracy. Various tools were used for evaluating the level of greenness, including Green Analytical Procedure Index (GAPI), Analytical Greenness Metric for Sample Preparation (AGREEprep), Analytical Eco-Scale (AES), and Analytical Method Greenness Score (AMGS). These tools had confirmed the eco-friendliness of the proposed method. Additionally, the newly introduced White Analytical Chemistry (WAC), and the Blue Applicability Grade Index (BAGI) have been specifically developed to evaluate the sustainability and the applicability of the method. [ABSTRACT FROM AUTHOR]

Aim: Hearing loss, affecting a significant portion of the global population, is prevented with peroxisome proliferator-activated receptor γ agonism. Understanding potential protective treatments is crucial for public health. We examine the effect of telmisartan, an antihypertensive drug and partial peroxisome proliferator-activated receptor γ agonist, on hearing loss in patients with hypertension. Method and results: This retrospective cohort analysis used data from the OMOP Common Data Model database, encompassing information from three tertiary institutions in South Korea. The study included a substantial sample size of 860,103 people diagnosed with hypertension. The study included individuals who had been medically diagnosed with hypertension and had been prescribed antihypertensive drugs, including telmisartan. The study design was established to evaluate the comparative effects of telmisartan and other hypertension medications on hearing loss. We used propensity score matching (PSM) to create a balanced cohort, reducing potential biases between the telmisartan and non-telmisartan groups. Fromthe initial 860,103 patients with hypertension, a propensity score matched cohort was derived from 20,010 patients, with 2,193 in the telmisartan group. After PSM, lower incidence of total hearing loss was observed in the telmisartan group compared to the non-telmisartan group during the 3-year follow-up (0.5% vs. 1.5%, log-rank p = 0.005). In subgroup analysis, this study showed consistent results that lower incidence of total hearing loss was higher in the telmisartan group than in the non-telmisartan group. Conclusion: Telmisartan was associated with reducing certain types of hearing loss in patients with hypertension. Further research is needed to confirm these findings and understand the mechanisms. [ABSTRACT FROM AUTHOR]

Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high‐resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three‐element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10−1) min·mL−1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10−1) min·mL−1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10−1) mmHg·min·mL−1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10−1) mmHg·min·mL−1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature. NEW & NOTEWORTHY: This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II. [ABSTRACT FROM AUTHOR]

Administrative claims databases often do not capture date or fact of death, so studies using these data may inappropriately treat death as a censoring event—equivalent to other withdrawal reasons—rather than a competing event. We examined 1-, 3-, and 5-year inverse-probability-of-treatment weighted cumulative risks of a composite cardiovascular outcome among 34 527 initiators of telmisartan (exposure) and ramipril (referent), who were aged ≥55 years, in Optum (United States) claims data from 2003 to 2020. Differences in cumulative risks of the cardiovascular endpoint due to censoring of death (cause-specific), as compared with treating death as a competing event (subdistribution), increased with greater follow-up time and older age, where event and mortality risks were higher. Among ramipril users, 5-year cause-specific and subdistribution cumulative risk estimates per 100, respectively, were 16.4 (95% CI, 15.3-17.5) and 16.2 (95% CI, 15.1-17.3) among ages 55-64 (difference = 0.2) and were 43.2 (95% CI, 41.3-45.2) and 39.7 (95% CI, 37.9-41.4) among ages ≥75 (difference = 3.6). Plasmode simulation results demonstrated the differences in cause-specific versus subdistribution cumulative risks to increase with increasing mortality rate. We suggest researchers consider the cohort's baseline mortality risk when deciding whether real-world data with incomplete death information can be used without concern. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Chronic viral infections caused by the human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common among patients with end-stage renal disease (ESKD). These infections were once considered contraindications to kidney transplantation due to potential risks associated with long-term immunosuppression. Improved management and antiviral therapies have changed the prognosis and survival of this group of patients, along with an increased experience in transplanting people with these viral infections. We report the first successful kidney transplant in an ESKD patient on hemodialysis with a history of concomitant HIV, HCV and HBV infection in Mexico. [ABSTRACT FROM AUTHOR]

The study explains the preparation of spherical agglomerates (SA) of telmisartan (TLS), a BCS class II drug used to improve it's physicochemical and bulk properties. Drugs of this class could potentially exhibit dissolution rate limited absorption. TLS spherical agglomerates were designed using hydrophilic polymer (PVP K-30), dimethyl formamide (DMF), water and ethyl acetate (bridging liquid) by solvent change method and evaluated for micromeritic properties. The SA were characterized by particle size determination, FTIR, PXRD and SEM. The results of micromeritic studies indicated that SA showed improved flow properties due to their spherical shape and bigger size. Absence of strong interaction at molecular level and alteration in the crystal structure of TLS with modification in crystallinity was confirmed by FTIR and PXRD respectively. TLS solubility characteristics were improved by this approach. [ABSTRACT FROM AUTHOR]

This study focuses on the development of a liposomal preparation for the targeted delivery of Telmisartan in the context of breast cancer treatment. Telmisartan, a pharmaceutical agent with potential anticancer properties, has been encapsulated within liposomes, lipid-based vesicles known for their capacity to enhance drug delivery and improve therapeutic outcomes. The formulation and characterization of Telmisartan-loaded liposomes were conducted, evaluating factors such as size, shape, and drug release profiles. The findings demonstrate that the liposomal preparation effectively encapsulates Telmisartan, maintaining its pharmacological properties. The development of such liposomal formulations holds promise for advancing breast cancer therapies, offering the potential for enhanced treatment efficacy and reduced side effects. This research contributes to the ongoing efforts to explore innovative drug delivery strategies in the realm of breast cancer treatment. Breast cancer is a pervasive and challenging malignancy affecting women worldwide. In the quest for more effective and targeted treatment approaches, the development of liposomal preparations for delivering therapeutic agents to breast cancer cells has emerged as a promising avenue. Telmisartan, originally recognized for its antihypertensive properties, has been increasingly investigated for its potential anticancer effects. This study delves into the design and evaluation of a liposomal formulation for Telmisartan, aiming to enhance its therapeutic potential in breast cancer. The formulation process involved the encapsulation of Telmisartan within lipid-based liposomes, which are wellknown for their ability to carry a variety of drugs, protect them from degradation, and enhance their selective delivery to tumor cells. [ABSTRACT FROM AUTHOR]

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF. [ABSTRACT FROM AUTHOR]

Essential hypertension can be treated with telmisartan, a strong, long-acting nonpeptide antagonist of angiotensin II type-1 (AT1) receptor. Without influencing other receptor systems involved in the regulation of the cardiovascular system, it specifically blocks the activation of the AT1 receptor by angiotensin II. When combined with high volume of distribution and telmisartan's distinctively high lipophilicity, the molecule provides the clinically significant benefit of strong tissue penetration. Additionally, it causes an increase in the protein level of adiponectin in adipocytes and activates peroxisome proliferatoractivated receptor c (PPAR-c). They might increase insulin sensitivity in this way. According to the BCS classification, it is class II medication because of its high permeability and low solubility. To increase the telmisartan solid dispersion's aqueous solubility and dissolution rate, various techniques were prepared and studied. One of the main issues with this medication is its low solubility in biological fluids, which leads to poor bioavailability after oral administration. Telmisartan's solubility was shown to be enhanced when the medication was dispersed solidly utilizing carrier such poly vinyl pyrrolidonek30, poly ethylene glycol 6000, βeta-cyclodextrin, Gelucire 43/01, Poloxamer 407, PVP K30 and HPMC E4, PEG 6000, and NaHCO3. [ABSTRACT FROM AUTHOR]

Background: Dispensed drugs stored by patients are often in single-dose packages (SDPs) or are crushed and mixed after being removed from a press-through package (PTP) sheet. Information on their stability is extremely limited. To address this, we explored using chemiluminescence (CL) measurements to detect oxidative degradation. Methods: Eight amlodipine, 14 telmisartan, and two warfarin preparations were used as specimens. These preparations were stored at room temperature under various conditions, after which CL was measured. Cellopoly packaging paper was used for SDP. Three light conditions were used (Condition A: darkness, Condition B: indoor diffused light (approximately 400 lx), and Condition C: exposure to 4,000 lx). CL cumulative light output was measured every minute under nitrogen gas conduction and with a sample chamber temperature of 150 °C, for a maximum of 10 min. Luminescence images were obtained simultaneously with the CL measurements. Results: CL was observed on light-exposed tablet surfaces. For each preparation, an increase in the CL value was observed with the duration of light exposure. In the same preparation with the same exposure time, CL tended to be higher in the order of Condition A < B < C. Moreover, CL increased even when no changes in color were observed by the naked eye. A comparison between preparations with the same main ingredients showed differences in the rate of increase in CL with exposure, and each was found to show a different reactivity to light. Conclusions: To the best of our knowledge, this is the first study to visually capture the surface oxidation of tablets exposed to light using the CL method. The CL values, thought to be derived from photooxidation, increased with exposure of tablets and powders to light after SDP. This method can sensitively assess drug degradation due to photooxidation. Further research is needed to establish a CL method for assessing the stability of preparations in clinical settings. [ABSTRACT FROM AUTHOR]

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for simultaneous quantification of Azelnidipine (AZN) and Telmisartan (TMN) in combined tablet dosage forms. Chromatographic separation was achieved using a C18 column (100 × 4.6 mm, 2.5 µm particle size) with a mobile phase consisting of Acetonitrile: pH 3 phosphate buffer (75:25, v/v) at a flow rate of 0.9 mL/min, with detection occurring at 237 nm. The method was validated according to International Conference on Harmonisation (ICH) guidelines, demonstrating linearity over the concentration ranges of 6.4-32 µg/mL for AZN and 16-80 µg/mL for TMN. The limits of detection (LOD) and quantitation (LOQ) were determined to be 0.4399 and 1.3332 for AZN, and 0.882 and 2.6729 for TMN, respectively. The method also exhibited precision, repeatability, and accuracy, with relative standard deviations (RSD) = 2% and accuracy ranging from 99-101%. To assess the method's stability-indicating capability, forced degradation studies were conducted under four stress conditions: acidic hydrolysis, alkaline hydrolysis, oxidative degradation, and thermal degradation. The results confirmed the method's ability to accurately quantify AZN and TMN in the presence of degradation products. [ABSTRACT FROM AUTHOR]

Background: Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body: Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion: Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions. [ABSTRACT FROM AUTHOR]

Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine (10 mg/kg) was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan (TEL; 5 and 15 mg/kg) orally by gavage 30 min before each morphine injection. L-NAME (10 mg/kg), L-arginine (L-ARG,300 mg/kg) or N-acetylcysteine (NAC, 50 mg/kg) was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while LNAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL (15 mg/kg) treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway. [ABSTRACT FROM AUTHOR]

Telmisartan, a selective inhibitor of angiotensin II receptor type 1 (AT1), demonstrates nonlinear pharmacokinetics (PK) when orally administered in ascending doses to healthy volunteers, but the underlying mechanisms remain unclear. This study presents a physiologically based pharmacokinetic model integrated with target‐mediated drug disposition (TMDD‐PBPK model) to explore the mechanism of its nonlinear PK. We employed the Cluster‐Gauss Newton method for top‐down analysis, estimating the in vivo Km,OATP1B3 (Michaelis–Menten constant for telmisartan hepatic uptake via Organic Anion Transporting Polypeptide 1B3) to be 2.0–5.7 nM. This range is significantly lower than the reported in vitro value of 810 nM, obtained in 0.3% human serum albumin (HSA) conditions. Further validation was achieved through in vitro assessment in plated human hepatocytes with 4.5% HSA, showing a Km of 4.5 nM. These results underscore the importance of albumin‐mediated uptake effect for the hepatic uptake of telmisartan. Our TMDD‐PBPK model, developed through a "middle‐out" approach, underwent sensitivity analysis to identify key factors in the nonlinear PK of telmisartan. We found that the nonlinearity in the area under the concentration–time curve (AUC) and/or maximum concentration (Cmax) of telmisartan is sensitive to Km,OATP1B3 across all dosages. Additionally, the dissociation constant (Kd) for telmisartan binding to the AT1 receptor, along with its receptor abundance, notably influences PK at lower doses (below 20 mg). In conclusion, the nonlinear PK of telmisartan appears primarily driven by hepatic uptake saturation across all dose ranges and by AT1‐receptor binding saturation, notably at lower doses. [ABSTRACT FROM AUTHOR]

Lipohypertrophy (LH) is a common side effect of insulin treatment in patients with diabetes, characterized by soft, benign nodules in the subcutaneous tissue. This case report describes the management of insulin‑induced LH in a 66‑year‑old male with type 2 diabetes. The patient had been on a combination of oral antidiabetic agents (ODAs) and biphasic human insulin for 5 years, experiencing the symptoms of numbness, leg swelling, fatigue, and frequent hypoglycemic episodes. Upon examination, LH with skin pigmentation was observed at the insulin injection sites on both calves. The patient’s laboratory investigations revealed poor glycemic control with high glycated hemoglobin percentage. To address the condition, the patient was advised to change the injection site, use proper site rotation, and change the insulin needle daily. The insulin therapy was modified by switching to biphasic premixed analog insulin injected 5 min before meals using the insulin pen. In addition, ODAs were adjusted for better glycemic control. Following these interventions, the patient reported improved glucose levels and stable kidney function. This case report emphasizes the importance of early detection and appropriate management of insulin‑induced LH through patient education and insulin therapy adjustments. Health‑care providers should remain vigilant for LH and educate patients on proper injection practices to optimize diabetes management and prevent complications. [ABSTRACT FROM AUTHOR]

IntroductionTreatment 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.MethodsSeven 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.ResultsWeight 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.DiscussionAs 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.