Pharmacology Research & Perspectives最新文献

{"title":"Colo-Protective Effects of Pentoxifylline Alone or in Combination With Mesalamine in Colitis Through Sphingosine Kinase 1/Sphingosine 1 Phosphate, and Zonula Occuldin 1 Pathways: New Molecular Approach.","authors":"Fatemah A Alherz, Mahmoud S Abdallah, Esraa M Mosalam, Mostafa M Bahaa, Thanaa A Elmasry, Mohamad A El-Gammal, Walaa A Negm, AyaIbrahim Elberri, Nora Elshorbagi, Hend E Abo Mansour, Amir O Hamouda, Muhammed M Salahuddin, Mohamed Yasser, Mamdouh Eldesoqui, Sarah Alrubia, Amsha S Alsegiani, Eman El-Khateeb, Mohamed Kh ElMahdy, Eman Wahsh","doi":"10.1002/prp2.70115","DOIUrl":"10.1002/prp2.70115","url":null,"abstract":"<p><p>Multiple signaling pathways have been implicated in the pathogenesis of ulcerative colitis (UC), including Sphingosine Kinase 1 (SPHK)/Sphingosine-1-Phosphate (S1P), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/NLR family pyrin domain-containing 3 (NLRP3), zonula occludens-1 (ZO-1), and signal transducer and activator of transcription 3 (STAT3). We aimed to investigate the Colo protective and anti-ulcerative effects of pentoxifylline (PTX) in a rat model of UC. Colitis was induced by intracolonic administration of 2 mL of 3% (v/v) acetic acid (AA). Thirty-five rats were randomly assigned to five groups (n = 7 each): normal control, colitis, mesalamine, PTX, and a combination of PTX plus mesalamine. Disease activity was assessed using the disease activity index, colon weight and length measurements, histological examination, and immunohistochemical detection of caspase-3. Colonic tissue homogenates were analyzed for interleukin-6 (IL-6), S1P, SPHK, mTOR, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), AMPK, and STAT3 levels. Gene expression of ZO-1 and NLRP3 was also evaluated. Intracolonic AA induced marked functional, biochemical, and inflammatory damage to colonic tissue. Treatment with PTX, mesalamine, or their combination significantly attenuated these effects. Specifically, all treatments reduced levels of IL-6, S1P, SPHK, mTOR, STAT3, NLRP3, and caspase-3, while increasing levels of ZO-1, HO-1, Nrf2, and AMPK. The combination treatment group exhibited near-complete restoration of normal colonic architecture, characterized by intact crypt morphology and minimal fibrosis in the lamina propria. PTX attenuated inflammation, apoptosis, and oxidative stress in colitis, supporting its potential as an adjuvant therapy in UC management.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70115"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costs of Treating Onasemnogene Abeparvovec-Xioi-Induced Liver Injury.","authors":"Andrej Belančić, Branislava Raičević, Ivana Stević, Dinko Vitezić, Slobodan M Janković","doi":"10.1002/prp2.70134","DOIUrl":"10.1002/prp2.70134","url":null,"abstract":"<p><p>Aims were to reveal types of onasemnogene abeparvovec-xioi (OA)-induced liver injury, their treatment patterns, utilization of healthcare, and treatment costs. This study employed secondary research to analyze OA-induced liver injury using data from the EudraVigilance database, published case reports, cohort studies, and clinical trials. The extracted data were analyzed to define real-life clinical entities that could be clearly outlined as syndromes resulting from the OA-induced liver injury, and further used in guiding the development of healthcare utilization matrices. Serbian healthcare costs were calculated by multiplying utilization figures by local unit prices, converted to Euros using exchange rates and adjusted by price level indices. A spreadsheet model with uniform distributions simulated costs for 1000 virtual patients, providing mean values and standard deviations for Serbia and the EU. From 1566 adverse event reports in the EudraVigilance database following OA therapy, 231 were hepatobiliary disorders, predominantly hypertransaminasaemia (30.7%; 71/231). Liver injury largely manifested as mild-to-moderate biochemical abnormalities, rarely progressing to severe complications, and was effectively managed with corticosteroid therapy. Economic analysis highlights the manageable burden of OA-induced liver injury. In the EU, mild-to-moderate cases cost €823.7, while severe cases average €1638.6. Medication costs range from €26.8 for prednisone to €695.4 for severe cases requiring additional immunosuppressive agents like tacrolimus and mycophenolate mofetil. To conclude, OA-induced liver injury, though notable, is clinically manageable with immunosuppressive therapy and rarely causes severe complications like encephalopathy or liver failure. Its modest costs do not undermine OA's cost-effectiveness, supporting its transformative role in spinal muscular atrophy treatment.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70134"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Medication Adherence to Tadalafil 5 mg Once Daily in Erectile Dysfunction: A Cross-Sectional Analysis.","authors":"Emre Kandemir, Onur Kucuktopcu","doi":"10.1002/prp2.70129","DOIUrl":"10.1002/prp2.70129","url":null,"abstract":"<p><p>Our study aimed to examine medication adherence (MA) to tadalafil 5 mg once daily (OaD) in patients undergoing treatment for erectile dysfunction (ED) and to identify factors contributing to potential drug noncompliance. This cross-sectional study included 233 patients diagnosed with ED. Sociodemographic and clinical data were recorded. MA was assessed using the Medication Adherence Report Scale (MARS). Additionally, the Brief Illness Perception Questionnaire (B-IPQ), the Beliefs about Medicines Questionnaire (BMQ), and the International Index of Erectile Function (IIEF) were employed to evaluate patients' perceptions and beliefs regarding their condition and treatment. The influence of these factors on MA was thoroughly analyzed. High MA was reported in 136 (58.4%) of 233 patients. Factors, such as education level, monthly income, frequency of medical examinations, smoking habits, and a history of radical pelvic surgery, were found to influence MA (p < 0.05) significantly. Multivariate analysis identified monthly income and radical pelvic surgery history as statistically significant predictors of adherence (p ≤ 0.05). Additionally, adherence was significantly associated with IIEF scores, five items on the B-IPQ, and the BMQ subscales, including specific concerns, necessity, and general harm (p < 0.05). Tadalafil OaD demonstrates acceptable rates of MA in the treatment of ED. Socioeconomic and clinical factors, patients' cognitive and sensory status, and perceptions regarding medications and healthcare providers significantly influence adherence. Physicians should exercise caution when prescribing tadalafil 5 mg OaD to patients with lower socioeconomic status, as they may be at higher risk for reduced MA.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70129"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Different Targeted Therapies in Patients With Moderate-to-Severe Ulcerative Colitis: Systematic Review/Network Meta-Analysis and Mechanistic Overview.","authors":"Youran Dai, Wenhui Yang, Li Xu, Pingting Pan, Shan Liu, Yingzhe Sun, Suying Hu, Qiushuang Li, Fang Hu","doi":"10.1002/prp2.70108","DOIUrl":"10.1002/prp2.70108","url":null,"abstract":"<p><p>Ongoing evaluations of targeted therapies for moderate-to-severe ulcerative colitis (UC) continue to unfold, with the emergence of novel drugs. However, head-to-head trials comparing these therapies are still lacking. The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate-to-severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty-three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45 mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83-20.80), clinical response (OR 7.96; 95% CI, 3.89-16.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36-23.62). Cobitolimod 250 mg was the first-ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108 mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000/500 mg. During the maintenance phase, Etrasimod 2 mg/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82-32.59), and Upadacitinib 45 mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200 mg (OR 3.04; 95% CI, 1.70-5.40). Consequently, there is a need for further high-quality research to conclusively determine the best therapeutic option.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70108"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study.","authors":"Jing Hu, Yuhan Zhao, Litao Shao, Wenhui Zhang, Han Wang, Yun Liu, Mengxiang Su, Xiangrong Zuo","doi":"10.1002/prp2.70130","DOIUrl":"10.1002/prp2.70130","url":null,"abstract":"<p><p>The pharmacokinetic (PK) profile of remimazolam, a ultra-short-acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single-center, double-blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24 h. Participants were divided into three groups, each receiving a 0.2 mg/kg remimazolam loading dose in less than a minute, followed by maintenance doses of 0.1, 0.3, or 0.5 mg/kg/h. Plasma concentrations of remimazolam and its metabolites were measured using UPLC-MS/MS, and pharmacokinetic parameters were calculated using one-compartmental methods with WinNolin. The study also assessed pharmacodynamic indicators (RASS score) and the impact of the clinical indicators on pharmacokinetic parameters. The study on 36 ICU patents using a one-compartment model found that after 24 h of continuous intravenous remimazolam infusion, the drug had a median clearance rate of 22.23 mL/kg/min and a volume of distribution of 2656.58 mL/kg. The half-life was 101.791 min in ventilated patients, while its metabolites had a slower clearance rate of 0.49 mL/kg/min and an longer half-life of 656.02 min. Sedation levels were mild to moderate at dosed of 0.1-0.3 mg/kg/h. Liver function significantly affected remimazolam metabolism, influencing the half-life (R² = 0.36, p = 0.00013) and clearance (R² = 0.13, p = 0.04). The pharmacokinetic study indicates that remimazolam is effective and safe for ICU patients on mechanical ventilation, with a 24-h infusion demonstrating rapid clarence and a clear dose-effect relationship. It provides mild to moderate sedation at 0.1-0.3 mg/kg/h, but caution is advised for patients with severe liver dysfunction due to its impact on drug metabolism. Trial Registration: ClinicalTrials.gov identifier: NCT05480787.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70130"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Encapsulation of Carvedilol in Nanomicelles Improves Central Hemodynamics and Target Organ Damage Protection in Spontaneously Hypertensive Rats.","authors":"Luciano Parola, Paula Denise Prince, Javier Alberto Walter Opezzo, Jennifer Riedel, Miguel Ángel Allo, Yanina Alejandra Santander Plantamura, Eliana P Bin, Germán E González, Andrea Carranza, Martín Donato, Diego A Chiappetta, Marcela A Moretton, Christian Höcht","doi":"10.1002/prp2.70125","DOIUrl":"10.1002/prp2.70125","url":null,"abstract":"<p><p>The hypothesis of this work was that chronic treatment with carvedilol (CAR) administered in a nanomicelles-based formulation (CAR-NMs), which increases CAR oral bioavailability, is more effective than a conventional liquid CAR formulation (CAR-LCF) and is comparable to chronic treatment with losartan (LOS) in improving hemodynamic parameters and preventing target organ damage (TOD) in spontaneously hypertensive (SH) rats. Chronic treatment with CAR-NMs significantly improved central hemodynamic parameters (systolic and diastolic blood pressure (BP) and its variability) to a similar extent as LOS, and with superior efficacy than CAR-LCF. Although LOS was more effective than CAR-NMs and CAR-LCF in reducing peripheral systolic BP, both LOS and CAR-NMs, in contrast to CAR-LCF, were able to significantly reduce short-term BP variability indexes. Both CAR formulations and LOS significantly reduced aortic media wall thickness and interstitial collagen deposition, and lowered TNF-α expression in left ventricle (LV) in SH rats. Only CAR-NMs significantly reduced IL-6 expression and were more effective in reducing ventricular TGF-β expression in LV of SH rats. These findings suggest that encapsulation of CAR in NMs improved its ability to control central hemodynamics in SH rats when compared with CAR-LCF, mainly due to a greater effect on carotid systolic BP and short-term BP variability, resulting in a higher protection against TOD compared to CAR-LCF.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70125"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessments of CYP-Inhibition-Based Drug-Drug Interactions Between Tofacitinib and Lipid-Lowering Agents in Rats Both In Vitro and In Vivo.","authors":"Hang Yang, Shuanghu Wang, Quan Zhou, Peiwu Geng, Zebei Lu, Qinrong Lin, Chunhong Chen, Yunfang Zhou, Jianping Cai, Dapeng Dai","doi":"10.1002/prp2.70127","DOIUrl":"10.1002/prp2.70127","url":null,"abstract":"<p><p>Tofacitinib is a widely used medication for the treatment of arthritis. It has been reported that some patients experience abnormal cholesterol levels following treatment, leading to recommendations for the coadministration of lipid-lowering drugs such as statins. In this study, we investigated the potential drug-drug interactions between tofacitinib and the statins simvastatin and lovastatin. In the in vitro experiments, rat liver microsomes were employed to evaluate the inhibitory effects of lipid-lowering agents on the metabolism of tofacitinib, with the primary metabolite M8 analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. The results showed that simvastatin and lovastatin significantly inhibited the metabolism of tofacitinib, with IC₅₀ values of 5.837 and 10.68 μM, respectively. For the in vivo pharmacokinetic studies, Sprague-Dawley rats were pretreated with simvastatin or lovastatin via oral gavage for 7 days before the oral gavage of tofacitinib. This pretreatment led to an increased area under the concentration-time curve of tofacitinib, suggesting that a potential reduction in the first metabolism and/or systemic clearance takes place. These findings demonstrate significant interactions between tofacitinib and certain lipid-lowering agents in the rat model, particularly simvastatin and lovastatin, both in vitro and in vivo.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70127"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring Serum Bisoprolol Concentrations in Patients With Heart Failure With Reduced Ejection Fraction: Results of a Pilot Study From Routine Health Care.","authors":"Ivana Kacirova, Marie Lazarova, Romana Urinovska, Jozef Dodulik, Diana Drienikova, Jan Vaclavik","doi":"10.1002/prp2.70089","DOIUrl":"10.1002/prp2.70089","url":null,"abstract":"<p><p>Bisoprolol is a second-generation, highly selective beta-1 adrenergic receptor antagonist with various beneficial effects in patients with heart failure. Interindividual variability in response to bisoprolol is known, and finding the optimal dose for individual patients with heart failure is still challenging. This pilot study included patients treated with bisoprolol for chronic heart failure with reduced ejection fraction. Between November 2022 and November 2023, one to six blood samples were collected from these patients to determine the trough serum concentration of bisoprolol. At the same time, the values of selected clinical variables were recorded. Bisoprolol concentrations ranged from 1.1 to 65.0 μg/L and correlated with both the daily dose and the dose per kilogram of body weight. However, wide variability in measured serum concentrations of bisoprolol was observed at the same daily dose and in apparent weight-adjusted clearance. Patients classified as NYHA III-IV received a 33% higher dose per kilogram of body weight than patients in NYHA I-II but achieved 165% higher serum concentrations of bisoprolol. An inverse correlation was found between diastolic blood pressure and dose per kilogram of body weight, and a positive correlation between N-terminal pro-B-type natriuretic peptide and both dose per kilogram of body weight and serum bisoprolol concentration. A wide variability in patients' serum concentrations of bisoprolol achieved after taking the same dose has been observed. A significantly higher concentration-to-dose ratio and a significantly lower weight-adjusted apparent clearance were demonstrated in patients with reduced cardiac function, reduced renal function, and taking the combination with amiodarone. These patients may be more prone to overdose with bisoprolol.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70089"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accounting for Time-Varying Confounding in a Self-Controlled Case Series of Fluoroquinolone Treatment for Uncomplicated Urinary Tract Infections and Risk of Collagen-Related Events.","authors":"Anna Schultze, Shinyoung Ju, Myriam Drysdale, George Mu, Fanny S Mitrani-Gold, John Logie","doi":"10.1002/prp2.70124","DOIUrl":"10.1002/prp2.70124","url":null,"abstract":"<p><p>We report findings from three SCCS conducted to quantify the association between fluoroquinolone (FQ) use for the treatment of uncomplicated urinary tract infection (uUTI) and tendon rupture, retinal detachment, and uveitis. Female patients aged ≥ 12 years old in the Optum Clinformatics Data Mart database with an outcome of interest and exposure to either oral FQ or trimethoprim/sulfamethoxazole (SXT) in the 5 days following a newly reported uUTI during the study period (01/01/2011-02/10/2019) were included. We considered a 90-day risk window for each outcome following drug exposure. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using conditional Poisson regression, adjusting for age and calendar time, incorporating SXT as an active comparator. We found little evidence of an association between FQ use compared to SXT and any of the outcomes of interest (tendon rupture: IRR = 1.01, 95% CI = 0.91-1.21; retinal detachment: IRR = 0.99, 95% CI = 0.86-1.14; and uveitis: IRR = 1.09, 95% CI = 0.97-1.22). Incorporating the active comparator using two different methods did not change conclusions. The lack of evidence for an association between short-term use of FQ and the comparator antibiotic (SXT) for the treatment of uUTI and collagen-related events also implies that there was no marked association between uUTI and these outcomes. However, power was limited, and a small increased risk cannot be ruled out. Using active comparators in SCCS can improve the robustness of studies of antibiotics and adverse events.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70124"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic Study of Anti-TB Drugs in the Native Ancestry Peruvian Population.","authors":"Luis Jaramillo-Valverde, Mary K Horton, Julio A Poterico, Cristina M Lanata, Heinner Guio","doi":"10.1002/prp2.70135","DOIUrl":"10.1002/prp2.70135","url":null,"abstract":"<p><p>In Peru, 33 113 individuals were diagnosed with tuberculosis (TB) in 2023. While TB treatments are generally effective, 3.4% to 13% of cases are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) being the most prevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in native Peruvian populations. This study aimed to determine the prevalence of TB drug-metabolizing genotypes in these populations. A cross-sectional analysis was conducted using genetic data from 254 participants from the Peruvian Genome Project (PGP) representing three subpopulations: Coast, Andes, and Amazon. Twenty-three genes associated with TB treatment, include isoniazid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differences were observed in genotype frequencies among subpopulations for AGBL4, NAT2, GSTP1, SLCO1B1, NOS, and CYP2B6 genes. The Amazonian population demonstrated a higher risk of DILI due to the increased prevalence of hepatotoxic alleles in AGBL4, GSTP1, and SLCO1B1. In contrast, alleles in the NOS gene indicated a lower risk of hepatotoxicity in the Andean population. However, the high-risk genotypes identified in the study's native Peruvian populations exhibit distinct prevalence patterns compared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeutic strategies to improve TB treatment outcomes among Peru's diverse subpopulations.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70135"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}