Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Assessments of protodioscin's antinociceptive and antidiarrheal properties: in vivo and in silico investigations on macromolecule binding affinity and modulatory effects.","authors":"Pompa Rani Ghosh, Md Sakib Al Hasan, Razina Rouf, Raihan Chowdhury, Balkrishnan Yadav, Emon Mia, Md Tanvir Islam, Md Rakibul Hasan, Siddique Akber Ansari, Irfan Aamer Ansari, Md Shimul Bhuia, Muhammad Torequl Islam","doi":"10.1007/s00210-025-03860-2","DOIUrl":"https://doi.org/10.1007/s00210-025-03860-2","url":null,"abstract":"<p><p>Protodioscin (PRO) is a furostanol saponin with antioxidant and anti-inflammatory properties. However, there is no proof against nociception and diarrhea. The study aims to investigate the antinociceptive and antidiarrheal effects of PRO, comparing its efficacy with diclofenac sodium (DFS) and loperamide (LOP) using in vivo and in silico methods. Antinociceptive activity was evaluated using the acetic acid-induced writhing and formalin-induced paw licking tests, and antidiarrheal effects were assessed via castor oil-induced diarrhea in mice. Mice were divided into groups receiving PRO (2.5 and 10 mg/kg, p.o.), DFS (25 mg/kg, p.o.), LOP (3 mg/kg, p.o.), or combinations. Molecular docking studies were conducted on COX-1, COX-2 enzymes, and the Mu-opioid receptor (MOR), with toxicity predictions performed for safety profiling. In vivo results demonstrated that PRO significantly (p < 0.05) reduced pain and diarrhea in animals. PRO at 10 mg/kg, showed comparable efficacy to DFS and LOP (25 and 3 mg/kg) in both models. Molecular docking revealed that PRO had stronger binding affinities with COX-1 (‒10.0 kcal/mol), COX-2 (‒9.6 kcal/mol) enzymes, and MOR (‒7.7 kcal/mol) compared to standard drugs. Toxicity predictions indicate PRO is relatively safe in some toxicity parameters. PRO exhibits significant antinociceptive and antidiarrheal activities comparable to DFS and LOP, making it a promising natural alternative for managing pain and diarrhea. Additional clinical trials and pharmacokinetic assessments are required to evaluate its long-term safety for use.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations on the sustainability of hypercholesterolemia treatment in the context of new drugs on the market: data from Campania, Italy.","authors":"Francesco Ferrara, Andrea Zovi, Roberto Langella, Angela Panico, Manlio Scognamiglio, Ugo Trama, Eduardo Nava, Maurizio Capuozzo, Ferdinando Primiano, Giuseppe Russo","doi":"10.1007/s00210-025-03862-0","DOIUrl":"https://doi.org/10.1007/s00210-025-03862-0","url":null,"abstract":"<p><p>Hypercholesterolemia is a major risk factor in the development of cardiovascular diseases. Statins have been the primary treatment for reducing LDL cholesterol for years; however, adverse events related to their use have led to the development of alternative therapies, such as ezetimibe, bempedoic acid, and PCSK9 inhibitors, including alirocumab, evolocumab, and inclisiran. The study is aimed at comparing the consumption and costs of lipid-lowering drugs in the first half of 2023 (21,446,011.54 DDD and 10,974,495.47 €) and 2024 (19,493,540.71 DDD and 12,260,634.95 €) to assess the economic impact of new therapies in the management of dyslipidemia and adherence to guidelines. Dispensing data, without access to patient data, were collected from private community pharmacies and hospital and district pharmacies. Drug consumption was measured using the ATC classification system and the defined daily dose (DDD). The study revealed a trend toward a reduction in the use of traditional statin monotherapy and an increase in more recent and combined therapies. Statins showed a significant reduction from 42% in the first half of 2023 to 30% in the first half of 2024. Combined therapies, such as statins with ezetimibe, showed no change in trend, maintaining a 17% share in both periods. New therapies, such as PCSK9 inhibitors, demonstrated an increase from 33% in the first half of 2023 to 40% in the first half of 2024, while bempedoic acid, either as monotherapy or in combination with ezetimibe, remained below 2%. In recent years, the treatment of dyslipidemia has seen the introduction of many therapeutic alternatives. Bempedoic acid, recently introduced and less expensive, when used as an adjunct therapy with statins and ezetimibe, could reduce side effects and improve therapeutic efficacy without immediately resorting to higher-cost injectable drugs such as evolocumab, alirocumab, and inclisiran. Monitoring prescription trends and costs is essential to maintain the sustainability of the healthcare system, enabling investments in innovation and effective therapies without waste.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pinosylvin as a promising natural anticancer agent: mechanisms of action and future directions in cancer therapy.","authors":"Phumudzo P Tshikhudo, Tafadzwanashe Mabhaudhi, Neil A Koorbanally, Fhatuwani N Mudau, Daniela Calina, Javad Sharifi-Rad","doi":"10.1007/s00210-025-03850-4","DOIUrl":"https://doi.org/10.1007/s00210-025-03850-4","url":null,"abstract":"<p><p>Cancer is a major global health challenge, with rising incidence necessitating alternative therapies. Pinosylvin, a natural phenolic compound in pine species, has demonstrated notable anticancer properties, making it a promising candidate for cancer treatment. This review synthesizes findings from extensive literature searches across databases, including PubMed and Scopus, to explore pinosylvin's efficacy against cancers like nasopharyngeal, prostate, colorectal, fibrosarcoma, and oral cancers. In vitro and in vivo studies indicate that pinosylvin disrupts cancer cell processes, such as migration and invasion, by targeting molecular pathways including MAPK, ERK, and PI3K. Its anti-inflammatory, antioxidant, and antimicrobial effects further support its therapeutic potential. Pinosylvin's anticancer mechanisms involve inhibiting cancer proliferation and metastasis while inducing apoptosis. These effects may be attributed to the compound's ability to modulate critical enzymes and pathways, underscoring its potential as a natural anticancer agent. However, further research, including clinical trials, is required to fully establish its efficacy and applicability in cancer treatment protocols.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel mechanistic insights of the potential role of gasotransmitters and autophagy in the protective effect of metformin against hepatic ischemia/reperfusion injury in rats.","authors":"Ahmed O Abdel-Zaher, Marwa H Bakr, Yomna H Gad, Alaa T Abdelhafez","doi":"10.1007/s00210-025-03837-1","DOIUrl":"https://doi.org/10.1007/s00210-025-03837-1","url":null,"abstract":"<p><p>Metformin exerts antidiabetic and pleiotropic effects. This study investigated the function and mechanisms of gasotransmitters and autophagy in the metformin-induced protection against ischemia/reperfusion injury (I/RI). According to measurements of serum hepatic function indicators and histopathological evaluation, metformin protected against hepatic I/RI-induced impairment of liver function and structure. In addition, metformin inhibited hepatic I/RI-induced hepatic oxidative stress, nitrosative stress, inflammation, and apoptosis. Also, it suppressed hepatic I/RI-induced decrease in hepatic heme oxygenase-1 (HO-1) and hydrogen sulfide (H₂S) levels and increase in nitric oxide (NO) production. Furthermore, metformin inhibited hepatic I/RI-induced decrease in protein expressions of endothelial NO synthase (eNOS), HO-1, cystathionine γ-lyase (CSE), and Beclin-1 and increase in the protein expression of inducible NO synthase (iNOS) in the liver tissue. Co-administration of the NO biosynthesis inhibitor, L-NAME, carbon monoxide(CO)-releasing molecule-A₁ (CORM-A₁), the H₂S donor, NaHS, or the autophagy stimulator, rapamycin (RAPA), enhanced all effects of metformin. The NO donor, L-arginine, the CO biosynthesis inhibitor, zinc protoporphyrin, the H₂S biosynthesis inhibitor, DL-propargylglycine, or the autophagy inhibitor, chloroquine (CQ), antagonized the effects of metformin. These findings reveal, for the first time, that increasing CO, H₂S, and autophagy levels with subsequent decreasing NO level play a critical role in metformin's protective action against hepatic I/RI. The ability of L-NAME, CORM-A₁, NaHS, and RAPA to boost metformin's protective effect in hepatic I/RI may positively be attributed to their ability to lower hepatic oxidative stress, nitrosative stress, inflammation, and apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quinoline derivative exerts antineoplastic efficacy against solid tumour by inducing apoptosis and anti-angiogenesis both in vitro and in vivo.","authors":"Pradeepa Kumar C, Banumathi, N D Satyanarayan, Sakshith Raghavendra Prasad, Rajeshwara N Achur, B T Prabhakar","doi":"10.1007/s00210-025-03830-8","DOIUrl":"https://doi.org/10.1007/s00210-025-03830-8","url":null,"abstract":"<p><p>Cancer is a heterogeneous and multicomplex disease with the highest morbidity and mortality rate. The targeting of tumour progression with drugs is a very well-established treatment strategy. Despite these, due to the failure of commonly used drugs in combating cancer, new drugs need to be screened and established for better therapeutic approach. With this rationale, the current investigation was aimed to develop quinoline compound (QC) derivatives as anti-tumour molecules. In this extended study, a series of QC analogues were subjected to anti proliferative assays through cell-based screening and evaluated its mechanism of action through apoptotic and anti-angiogenic assays. The change in cell behaviour was assessed through gene expression analysis using qRT-PCR and immunoblot analysis. Further, in vivo solid tumour model was developed and the anti-tumour potential of QC-4 was verified with gene expression studies. The results suggested that QC-4 exhibited significant cytotoxic effect, particularly against human lung adenocarcinoma cell lines and murine Ehrlich Ascites Carcinoma cells. The QC-4 induced condensation, nuclear damage and changes in membrane integrity resulted in apoptosis and neovascularisation inhibition. The modulation of apoptotic and angiogenic genes such as BAX, BAD, p53 and MMP-2 and 9 further supported the molecular cause of cytotoxicity induced by QC-4. The regression of in vivo solid tumour with extended survivability warranted the in vitro results and the gene expression patterns were additionally supportive. Overall, the QC-4 analogue exhibits the anti-neoplastic with a multi-target approach, reserving its capacity to be developed into a new class of the anticancer molecules.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy and safety of low-dose triple combination for hypertension treatment: a systematic review and meta-analysis of randomized controlled trials.","authors":"Mohamed S Elgendy, Hosam I Taha, Ahmed Mazen Amin, Yehya Khlidj, Mohamed R Ezz, Mohamed A Elgamasy, Ahmed Almezaine, Mohamed A Faheem, Islam Rajab, Mohamed Abuelazm","doi":"10.1007/s00210-025-03790-z","DOIUrl":"https://doi.org/10.1007/s00210-025-03790-z","url":null,"abstract":"<p><p>Recently, Low-dose triple single-pill combinations (LDTC) have become a promising option for managing hypertension. This review evaluates LDTC's effectiveness and safety versus standard care, monotherapy, and placebo for blood pressure (BP) control. A systematic review and meta-analysis of randomized controlled trials retrieved from PubMed, EMBASE, WOS, Scopus, and Cochrane from inception to September 2024. The analysis presented risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). PROSPERO ID: CRD42024595331. We identified five eligible trials with a total of 1,709 patients. LDTC had a higher rate of achieving BP < 140/90 at 4 to 6 weeks (wk) (RR: 1.56; CI: 1.41, 1.72; p < 0.01) and at 8 to 12 wk (RR: 1.43; CI: 1.31, 1.57; P < 0.01). Additionally, LDTC significantly reduced the automated office systolic BP at 4 to 6 wk (MD: -8.80; CI: -10.16, -7.44; p < 0.01), 8 to 12 wk (MD: -8.30; CI: -11.18, -5.42; P < 0.01), and at 24 wk (MD: -6.94; CI: -10.56, -3.32; P < 0.01). However, LDTC indicated an increased rate of hypokalemia (RR: 2.25; CI: 1.50, 3.38; P < 0.01), with no difference between both groups in total adverse events (AEs) (P = 0.44), serious AEs (P = 0.79), treatment discontinuation due to AEs (P = 0.91), and the AEs of special interest (P = 0.54). LDTC therapy is effective and safe for hypertension management but poses potassium depletion. Further large-scale studies are essential to confirm its clinical benefits.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutin engages opioid/benzodiazepine receptors towards anti-neuropathic potential in a rat model of chronic constriction injury: relevance to its antioxidant and anti-inflammatory effects.","authors":"Kimia Zamani, Sajad Fakhri, Amir Kiani, Fatemeh Abbaszadeh, Mohammad Hosein Farzaei","doi":"10.1007/s00210-025-03842-4","DOIUrl":"https://doi.org/10.1007/s00210-025-03842-4","url":null,"abstract":"<p><p>Neuropathic pain is a chronic type of pain caused by damage or dysfunction in the nervous system. It can be quite bothersome and often doesn't well respond to common painkillers. Among natural compounds, rutin (Rut) stands out for its remarkable antioxidant, and anti-inflammatory properties. In this research, our objective is to investigate the impact of Rut on an animal model of chronic constriction injury (CCI). A total of 54 adult Wistar rats were divided randomly into nine separate groups. Groups included sham, CCI, gabapentin (GBP, 100 mg/kg), Rut (10, 25 mg/kg), flumazenil (FLU, 0.5 mg/kg), naloxone (NAL, 0.1 mg/kg), Rut (10 mg/kg) + FLU (0.5 mg/kg), and Rut (10 mg/kg) + NAL (0.1 mg/kg). The aforementioned drug injection (intraperitoneal, i.p.) and sensorimotor behavioral tests were performed on days 1, 3, 5, 7, 9, 11, and 14. Biochemical (e.g., nitrite, catalase, glutathione), zymography (matrix-metalloproteinase 2 and 9), and histopathological tests were performed on day 14 after surgery. The findings demonstrated that Rut administration effectively alleviated symptoms of allodynia/hyperalgesia, and improved locomotor activity following CCI. Additionally, Rut administration resulted in increased catalase and glutathione activity, while reducing serum nitrite levels, as well as matrix metalloproteinase 2 and 9 activity. Additionally, histological results indicated that Rut improved sciatic nerve regeneration. Since the aforementioned effects of Rut were reversed by using opioid and benzodiazepine receptor antagonists (i.e., NAL and FLU, respectively), the receptors' involvement was revealed in the anti-neuropathic effects of Rut. In conclusion, Rut emerged as a potentially effective candidate for treating neuropathic pain and improving motor function by increasing antioxidant mediators, suppressing inflammation, and activating opioid/benzodiazepine receptors.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced inflammatory and oxidative response mitigation by acetyl-L-carnitine in a rat model of pelvic inflammatory disease.","authors":"Sidra Sultan, Ushna Zoofeen, Inayat Shah, Syed Murtaza Shah Bukhari, Naveed Sharif, Syed Kazim Shah Bukhari, Momin Khan, Syed Hamid Habib, Fawad Ali Shah, Mariam K Alamoudi, Mohsin Shah","doi":"10.1007/s00210-025-03858-w","DOIUrl":"https://doi.org/10.1007/s00210-025-03858-w","url":null,"abstract":"<p><p>Acetyl-L-carnitine (ALC) is known for its potent antioxidant and anti-inflammatory properties. This research aimed to investigate the properties of ALC in combating pelvic inflammatory disease (PID) in a rat model. PID, a consequence of sexually transmitted infections in females, can impact the fallopian tubes and uterus, leading to complications. This study is a randomized control preclinical experiment. A total of 24 reproductively mature Sprague Dawley female rats were randomly and equally assigned (n = 4 per group) to six cohorts: control, PID, low-dose prophylactic, high-dose prophylactic, and low-dose therapeutic and high-dose therapeutic groups. PID was induced by injecting the rat cervix with a multi-pathogen solution. Acetyl-L-carnitine, 100 mg/kg (once a day), was orally administered to rats in the low-dose prophylactic group, while 200 mg/kg (once a day) to the high-dose prophylactic group, starting 1 day prior to induction of PID. The therapeutic groups were given similar doses of ALC 1 day after the PID model was confirmed. Samples from the right upper genital tract were collected for ELISA and antioxidant assays, while the left upper genital tract samples underwent histopathological analysis. According to the results, the ALC-treated groups showed a decreased level of cytokines (IL-1β, TNF-α) and oxidative stress markers (catalase, lipid peroxidation) when compared to the PID group. Histopathological examinations revealed that ALC treatment reduced the infiltration of neutrophils and lymphocytes in the uterus compared to the PID group. It was concluded that ALC showed potential antioxidant and anti-inflammatory effects in PID and, therefore, could be used as a possible option for the treatment of PID.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of traditional herbal plants and their polyphenols in alleviation of mercury toxicity.","authors":"Saloni Agarwal, Swati Kaushik, Hiranmoy Saha, Debashish Paramanick, Mohd Mazhar, Parakh Basist, Rahmuddin Khan, Abdulsalam Alhalmi","doi":"10.1007/s00210-025-03807-7","DOIUrl":"https://doi.org/10.1007/s00210-025-03807-7","url":null,"abstract":"<p><p>Mercury (Hg) is a major environmental contaminant significantly impacting human health. As a naturally occurring element, mercury has been extensively mobilized into aquatic and terrestrial ecosystems over thousands of years, largely due to anthropogenic activities such as mining and metal extraction. Acute mercury toxicity causes extensive physiological damage, affecting vital organs including the kidneys, heart, liver, brain, and skin. Phytochemicals, known for their diverse pharmacological properties, have shown promise in mitigating metal-induced toxicities, including mercury. These compounds exhibit protective effects against mercury-induced multi-organ damage through mechanisms such as reactive oxygen species (ROS) scavenging, cyclooxygenase (COX) inhibition, and anti-inflammatory activity. This review explores the therapeutic potential of traditional herbal plants and their phytoconstituents in alleviating mercury-induced toxicity. Key findings highlight several plants with hepatoprotective effects, mitigating necrosis and anatomical distortion in liver cells. Phytochemicals such as quercetin, rutin, salicylic acid, ferulic acid, 6-gingerol, and 6-shogaol play pivotal roles in downregulating molecular pathways activated by mercury exposure. Other bioactive compounds, including acetogenin and gallic acid, exhibit potent antioxidant properties, with mechanisms such as ROS scavenging and inhibition of lipid peroxidation. This review also highlights certain compounds, such as aloe-emodin and gentisic acid, which exhibit potential for mitigating mercury toxicity through mechanisms like inhibiting oxidative stress and enhancing cellular defense pathways. However, these compounds remain underexplored, with no significant studies conducted to evaluate their efficacy against mercury-induced toxicity, presenting a critical area for future research. These findings underscore the potential of phytochemicals as effective agents in combating mercury toxicity through antioxidant mechanisms, cellular signalling regulation, and heavy metal chelation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic comparison of a fixed-dose combination of telmisartan/rosuvastatin/ezetimibe/amlodipine 80/20/10/5 mg and a loose-dose combination of ezetimibe/rosuvastatin 10/20 mg and telmisartan/amlodipine 80/5 mg in healthy male subjects.","authors":"Sooyoun Lee, Hyun Chul Kim, Kyung Tae Kim, Seung-Hyun Kang, SeungHwan Lee, Kyung-Sang Yu, Soyoung Lee","doi":"10.1007/s00210-025-03863-z","DOIUrl":"https://doi.org/10.1007/s00210-025-03863-z","url":null,"abstract":"<p><p>This study aimed to compare the pharmacokinetic (PK) profiles of a fixed-dose combination (FDC) tablet of telmisartan/rosuvastatin/ezetimibe/amlodipine 80/20/10/5 mg and a loose-dose combination (LDC) of two FDC tablets, ezetimibe/rosuvastatin 10/20 mg and telmisartan/amlodipine 80/5 mg, in healthy Korean male subjects. This study was conducted as a randomized, open-label, two-sequence, four-period crossover study. The subjects received the FDC or the LDC of telmisartan, rosuvastatin, ezetimibe, and amlodipine twice, with a 21-day washout in each period. Each sequence was composed of either FDC/LDC/FDC/LDC or LDC/FDC/LDC/FDC in that order. Serial blood samples for PK analysis were collected up to 48 h after rosuvastatin dosing and 72 h after telmisartan, ezetimibe, and amlodipine dosing. The PK parameters were calculated by a noncompartmental method, and safety profiles were evaluated throughout the study. Fifty-four healthy Korean male subjects were enrolled, and 42 subjects completed the study. The concentration‒time profiles of telmisartan, rosuvastatin, ezetimibe, and amlodipine were similar between the FDC and LDC groups. For each compound, the geometric mean ratios (90% confidence intervals) of the peak concentration and area under the plasma concentration‒time curve of FDC to LDC were within the conventional bioequivalence criteria of 0.8-1.25. Both the FDC and LDC treatments were well tolerated and determined to be safe. The FDC and LDC treatments with telmisartan, rosuvastatin, ezetimibe, and amlodipine showed pharmacokinetic bioequivalence, indicating that the FDC of telmisartan/rosuvastatin/ezetimibe/amlodipine 80/20/10/5 mg can be used as an alternative to the LDC treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}