Xenobiotica最新文献_第2页

Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders. NXE0041178的临床前药代动力学、代谢和处置，这是一种新型口服GPR52受体激动剂，具有治疗精神分裂症和相关精神疾病的潜力。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-19 DOI: 10.1080/00498254.2025.2501593

Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney

{"title":"Preclinical pharmacokinetics, metabolism, and disposition of NXE0041178, a novel orally bioavailable agonist of the GPR52 receptor with potential for treatment of schizophrenia and related psychiatric disorders.","authors":"Simon Poulter, Nigel Austin, Stephen P Watson, Sarah J Bucknell, M Alistair O'Brien, Ari Tolonen, Toni Lassila, Lisa A Stott, Andy Mead, Cliona MacSweeney","doi":"10.1080/00498254.2025.2501593","DOIUrl":"10.1080/00498254.2025.2501593","url":null,"abstract":"The physico-chemical properties, protein binding, metabolism, permeability, transporter interactions, chemical toxicity, and drug-drug interaction potential of the novel GPR52 agonist NXE0041178 were characterised.NXE0041178 demonstrated high cellular permeability, little interaction with efflux transporters P-gp and BCRP, and extensive brain exposure in rodent, consistent with its intended use in CNS disorders.In vivo pharmacokinetic profiling in mouse, rat and monkey demonstrated that NXE0041178 was well-absorbed, with low clearance, a moderate volume-of-distribution and moderate terminal half-life. Oxidative metabolism was the major elimination pathway, with negligible renal or biliary excretion.NXE0041178 displayed good in vitro-to-in vivo correlation in metabolic clearance in preclinical species and low turnover in human in vitro metabolic systems, suggestive of a human pharmacokinetic profile commensurate with once-daily dosing.Early in vitro metabolite identification studies suggested similar metabolic pathways in human and preclinical species, but a distinct metabolic profile in dog.NXE0041178 caused weak heterotropic catalytic activation of CYP3A4, and weak transcriptional induction of CYP3A4 and CYP2B6. No reactive metabolites of NXE0041178 were detected, and no genotoxicity or clinically relevant inhibition of P450 enzymes were observed.These findings extend our knowledge of the preclinical ADME profile of NXE0041178, supporting its continued development.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-16"},"PeriodicalIF":1.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080807","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}

引用次数: 0

LC-MS/MS determination of 27 antipsychotics and metabolites in plasma for medication management monitoring. LC-MS/MS测定血浆中27种抗精神病药物及其代谢物用于用药管理监测。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-15 DOI: 10.1080/00498254.2025.2498702

Shanshan Chen, Donghan Wang, Yuanyuan Zhao, Yaqi Sun, Yueyao Luan, Qixuan Sun, Jiaqi Wang, Yuhang Yan, Jing Yu, Chunhua Zhou

{"title":"LC-MS/MS determination of 27 antipsychotics and metabolites in plasma for medication management monitoring.","authors":"Shanshan Chen, Donghan Wang, Yuanyuan Zhao, Yaqi Sun, Yueyao Luan, Qixuan Sun, Jiaqi Wang, Yuhang Yan, Jing Yu, Chunhua Zhou","doi":"10.1080/00498254.2025.2498702","DOIUrl":"10.1080/00498254.2025.2498702","url":null,"abstract":"With the increasing prevalence and escalating complexity of mental disorders, precise medication has become critically important. This necessitates an efficient, accurate, and convenient method for drug concentration monitoring to support laboratory personnel and clinicians. In this study, three liquid chromatography-tandem mass spectrometry methods were developed and validated for simultaneously determining and quantifying 27 antipsychotics and related metabolites in human plasma. The plasma samples were subjected to protein precipitation using methanol, with isotope-labelled internal standards (ISs), followed by separation via isocratic elution on a BEH C18 column. Mass spectrometric analysis was performed using electrospray ionisation in positive ionisation mode with multiple reaction monitoring for quantitative detection. The analytes demonstrated high separation efficiency, with a single sample run time of 3.0 min. The method exhibited a wide linear range with excellent linearity across the concentration range. The intra- and inter-batch precision were ≤10.00%, the accuracy was 88.67-113.29%. Accurate quantification of antipsychotics remained unaffected under various storage conditions: 72 h at room temperature, 7 d at 4 °C refrigeration, and 14 d at -80 °C freezing. This validated methodology has been successfully applied to plasma samples from patients with psychiatric disorders, demonstrating its practical utility for accurate quantification of antipsychotics in large-scale and complex matrices containing multiple analytes.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052551","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}

引用次数: 0

Regulatory Effect of Atorvastatin combined with Berberine on PI3K/Akt/FoxO1 Signaling Pathway in Rats with Hyperlipidemia. 阿托伐他汀联合小檗碱对高脂血症大鼠PI3K/Akt/ fox01信号通路的调控作用

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-12 DOI: 10.1080/00498254.2025.2503359

Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui

{"title":"Regulatory Effect of Atorvastatin combined with Berberine on PI3K/Akt/FoxO1 Signaling Pathway in Rats with Hyperlipidemia.","authors":"Chao Yu, Weihong Yin, Jiao Li, Fan Wu, Siwen Wang, Zhaoyang Han, Haoliang Chen, Xueying Yan, Mingyu Cui","doi":"10.1080/00498254.2025.2503359","DOIUrl":"https://doi.org/10.1080/00498254.2025.2503359","url":null,"abstract":"1.Atorvastatin Calcium (AC) is the first line lipid-lowering drug in clinical. Nowadays, the combination of AC and BBR is often used to treat hyperlipidemia in clinical. In order to determine the mechanism, we investigate the regulatory of atorvastatin combined with berberine on PI3K/Akt/FoxO1 signaling pathway in rats with hyperlipidemia.2.The hyperlipidemia rat model was constructed. Meanwhile, lipid-lowering and liver protective effects were determined by oil red O and H&E method. The expression of PI3K, Akt and FoxO1 was examined by IHC, WB and RT-pCR. The level of CK and LDH in serum was examined by ELISA.3.The results showed that the expression of PI3K, AKT increased and FoxO1 decreased in MC group compared with NC group (P < 0.01). The expression of PI3K, AKT decreased and FoxO1 increased compared with MC group (P < 0.05). The expression of FoxO1 in combination group is lower than AC group. The levels of CK and LDH in AC group increased compared with NC group (P < 0.01), but decreased significantly in AC + BBR group compared with AC group(P < 0.01).4.The combination of AC and BBR could regulate the lipid level by mediating PI3K/Akt/FoxO1, which providing a new references for the treatment of hyperlipidemia.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050899","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}

引用次数: 0

Degradation studies on lurasidone hydrochloride using validated reverse phase HPLC and LC-MS/MS. 反相高效液相色谱法和LC-MS/MS法研究盐酸鲁拉西酮的降解。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-12 DOI: 10.1080/00498254.2025.2498699

Tanvi Kadam, Surendra Agarwal, Saritha Shetty

{"title":"Degradation studies on lurasidone hydrochloride using validated reverse phase HPLC and LC-MS/MS.","authors":"Tanvi Kadam, Surendra Agarwal, Saritha Shetty","doi":"10.1080/00498254.2025.2498699","DOIUrl":"https://doi.org/10.1080/00498254.2025.2498699","url":null,"abstract":"1. The research aims to develop and validate a stability-indicating reverse phase high-performance liquid chromatography (RP-HPLC) method for Lurasidone hydrochloride, an antipsychotic drug derived from benzisothiazole derivatives.2. A Binary Gradient HPLC System with a PDA detector, C18 column (4.6 x 100 mm, 2.5 mm), and a Shimadzu 8040 series triple quadrupole mass analyzer with an electron spray ionizer was used for the LC-MS/MS analysis.3. The method was linear in the concentration range of 10-50 μg/mL with a correlation coefficient (r2) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 0.091 μg/mL and 0.275 μg/mL, respectively. Validation included accuracy, percentage recovery, robustness, system suitability, and interday and intraday precision. Forced degradation studies were conducted in acid, alkali, oxidative, neutral, and photolytic conditions after 1, 2, and 6 hours, and in oxidative conditions for 24 hours. Degraded products were evaluated on LC-MS (100 m/z to 550 m/z). Lurasidone was more susceptible to alkali hydrolysis, with fragmentation peaks at 109, 166, 220, and 317 m/z. and possible fragmentation pattern was also evaluated.4. This method is used for routine quality control analysis as a stability-indicating method of Lurasidone hydrochloride in pharmaceuticals, and the LC-MS data is used for evaluating stability and identifying drug intermediates.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012958","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}

引用次数: 0

Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes. 大麻二酚体外代谢：抗癫痫药物和CYP2C19基因型的作用。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-10 DOI: 10.1080/00498254.2025.2498696

Nattapon Jaisupa, Michael Ashton, Sofia Birgersson

{"title":"Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes.","authors":"Nattapon Jaisupa, Michael Ashton, Sofia Birgersson","doi":"10.1080/00498254.2025.2498696","DOIUrl":"https://doi.org/10.1080/00498254.2025.2498696","url":null,"abstract":"1. Cannabidiol (CBD) can be used as add-on antiseizure medication. We aimed to investigate CBD depletion kinetics when combined with antiseizure medications, further the effect of intermediate-activity CYP2C19 genotype on CBD metabolism.2. CBD depletion in pooled human liver microsomes (HLMs) was studied at varying concentrations (400-6000 nM) in the absence and presence of valproic acid, clobazam, stiripentol and topiramate. In addition, CBD metabolism in HLMs from CYP2C19 *1/*2 or *1/*4 donors was investigated. Incubation samples were analysed for CBD and metabolites 7-OH-CBD and 7-COOH-CBD using LC-MS/MS. CBD in vitro intrinsic clearance (CLint) was calculated using estimated Vmax and Km values and further extrapolated to in vivo CLint.3. In vitro CLint values were reduced by approximately 25-85% in the presence of antiseizure medication(s) with the largest effect observed for the combination of four antiseizure drugs. There was no discernible difference for HLMs with CYP2C19 *1/*2 or *1/*4 genotype. Increases in CBD depletion half-lives at higher concentrations indicated substrate inhibition and/or metabolic saturation.4. Projected decreases in CBD CLint values when combined with several antiseizure medications suggest a potential for clinically relevant drug-drug interactions. A 1.3- to 4.8-fold increased exposure to unbound systemic CBD concentrations was predicted when combined with these antiseizure medications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026538","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}

引用次数: 0

Effectiveness of pain care intervention combined with traditional Chinese medicine care in the perioperative care of patients with urinary stones. 疼痛护理干预结合中医护理在泌尿系结石患者围手术期护理中的效果。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-08 DOI: 10.1080/00498254.2025.2494651

Binglei Yuan

{"title":"Effectiveness of pain care intervention combined with traditional Chinese medicine care in the perioperative care of patients with urinary stones.","authors":"Binglei Yuan","doi":"10.1080/00498254.2025.2494651","DOIUrl":"https://doi.org/10.1080/00498254.2025.2494651","url":null,"abstract":"The study investigated the effectiveness of pain care intervention combined with traditional Chinese medicine (TCM) care in the perioperative care of patients with urinary stones.Pain and urinary function recovery before and after postoperative care intervention, and Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) scores before and after care intervention in the two groups were compared. First anal discharge time, catheter retention time, first out of bed activity time, the total number of hospital days, and complications were observed in both groups after surgery, and the satisfaction scores of patients in both groups with the perioperative care were recorded.Compared with the control group, the observation group showed lower first anal discharge time, catheter retention time, first out of bed activity time, the total number of hospital days, and the incidence of complications after surgery, and the patients were more satisfied with the care.Pain care intervention combined with TCM care is beneficial in reducing postoperative pain in patients undergoing urinary stone surgery, speeding up the recovery of urinary function, improving sleep quality, anxiety, and depression, and reducing the incidence of complications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-7"},"PeriodicalIF":1.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038311","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}

引用次数: 0

Prediction of the neurotoxic mechanisms of the pesticide phorate using network toxicology, molecular docking, and molecular dynamics simulation. 应用网络毒理学、分子对接、分子动力学模拟等方法预测农药膦的神经毒性机制。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-05 DOI: 10.1080/00498254.2025.2498010

Jiahui Xu, Yinghao Xiao, Jixin Li, Zhongyi Liu, Lili Zhang, Wei Xu

{"title":"Prediction of the neurotoxic mechanisms of the pesticide phorate using network toxicology, molecular docking, and molecular dynamics simulation.","authors":"Jiahui Xu, Yinghao Xiao, Jixin Li, Zhongyi Liu, Lili Zhang, Wei Xu","doi":"10.1080/00498254.2025.2498010","DOIUrl":"https://doi.org/10.1080/00498254.2025.2498010","url":null,"abstract":"Phorate is an organophosphate pesticide that may cause neurotoxicity, although the exact mechanisms remain unclear.This study aimed to elucidate the mechanisms of neurotoxicity caused by phorate overexposure using network toxicology, molecular docking, and molecular dynamics simulation.We identified 104 potential targets and 20 core targets associated with phorate-induced neurotoxicity. Key targets, including MMP9, CASP1, and KEAP1, may be involved in neuroactive ligand-receptor interaction signalling, as well as the cAMP and calcium signalling pathways. Furthermore, molecular dynamics simulations were conducted on the KEAP1 and CASP1 protein-ligand complexes, which demonstrated the highest binding stabilities in molecular docking analysis. The binding free energies were calculated to be -27.08 and -22.80 kcal/mol for KEAP1 and CASP1, respectively, indicating that both complexes are thermodynamically stable.The methodology used in this study facilitates the identification and assessment of previously unexplored agrochemical toxicity pathways and molecular mechanisms. These findings suggest a novel approach to controlling pesticide residues and screening drugs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988985","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}

引用次数: 0

Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species. 基于特征的分子网络更新了芬苯达唑跨物种的体外代谢特征。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-04 DOI: 10.1080/00498254.2025.2497047

Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim

{"title":"Feature-based molecular networking updates the in vitro metabolic characterisation of fenbendazole across species.","authors":"Young-Heun Jung, Dong-Cheol Lee, Bo-Hyun Choi, Junyoung O Park, Ju-Hyun Kim","doi":"10.1080/00498254.2025.2497047","DOIUrl":"https://doi.org/10.1080/00498254.2025.2497047","url":null,"abstract":"1. Feature-based molecular networking (FBMN), an advanced metabolomics tool leveraging MS/MS spectral similarity, was applied to update metabolite characterisation of fenbendazole (FBZ), a veterinary antiparasitic agent with emerging anticancer potential in humans. Despite its therapeutic promise, FBZ's human metabolic pathways remain poorly understood.2. In this study, FBMN was utilised for the comprehensive in vitro profiling of FBZ metabolites across species, employing high-resolution liquid chromatography-mass spectrometry (LC-HRMS) with data-dependant MS2 acquisition.3. Nine metabolites, including two novel sulphate-conjugated forms (M2 sulphate and M7 sulphate), were identified and structurally characterised through integrated FBMN analysis. Oxidative metabolites (M1-M4) were found to be more abundant in rat liver microsomes, whereas monkey hepatocytes exhibited higher levels of most metabolites. Notably, hydrolysed FBZ (M5) dominated human samples, accounting for the largest proportion in both liver microsomes and hepatocytes, suggesting species-specific enzymatic activity.4. The application of FBMN provided an enhanced, systematic approach for metabolite identification and inter-species comparison, revealing critical metabolic differences that support FBZ biotransformation. These findings offer novel insights into FBZ's metabolic pathways, supporting its safety and efficacy assessment for potential human therapeutic applications.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050519","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}

引用次数: 0

Inhibition of YAP can down-regulate NLRP3 inflammasome and improve anti-tuberculosis drug-induced liver injury. 抑制YAP可下调NLRP3炎性体，改善抗结核药物性肝损伤。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-04 DOI: 10.1080/00498254.2025.2497050

Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng

{"title":"Inhibition of YAP can down-regulate NLRP3 inflammasome and improve anti-tuberculosis drug-induced liver injury.","authors":"Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng","doi":"10.1080/00498254.2025.2497050","DOIUrl":"https://doi.org/10.1080/00498254.2025.2497050","url":null,"abstract":"Yes-associated protein (YAP) is a core effector molecule in the Hippo signalling pathway, but its role in antituberculosis drug-induced liver injury (ADLI) is unclear. We aimed to explore the regulatory effects of YAP on the NLRP3 inflammasome in ADLI and its potential hepatoprotective effects.An ADLI animal model was established. Various indicators of experimental animals were detected at 0, 7, 14, and 21 days. On day 7, HE staining observed liver tissue, and liver index, ALT, and AST levels confirmed the ADLI model. YAP's mRNA and protein levels were examined, YAP inhibitor effects were observed, and NLRP3 inflammasome, inflammation, and oxidative stress indicators were analysed.It was found that the mRNA and protein levels of YAP increased during ADLI and then decreased due to the action of YAP inhibitors. YAP caused an elevation in NLRP3 inflammasome indicators, as well as increased expression of inflammation and oxidative stress. After feeding with YAP inhibitors, these indicators were reduced.The results suggest that targeting YAP may be a novel therapeutic strategy for alleviating antituberculosis drug-induced liver injury.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018497","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}

引用次数: 0

Pharmacokinetics and tissue distribution of intranasal administration of rapamycin in rats. 大鼠鼻内给药雷帕霉素的药代动力学和组织分布。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-05-04 DOI: 10.1080/00498254.2025.2498009

Anqi Yang, Zhe Hu, Chengyu Hu, Jiayi Liu, Jianchen Fan, Lifen Gong, Liqun Jiang, Xin Huang, Yicheng Xie, Jia Liu

{"title":"Pharmacokinetics and tissue distribution of intranasal administration of rapamycin in rats.","authors":"Anqi Yang, Zhe Hu, Chengyu Hu, Jiayi Liu, Jianchen Fan, Lifen Gong, Liqun Jiang, Xin Huang, Yicheng Xie, Jia Liu","doi":"10.1080/00498254.2025.2498009","DOIUrl":"https://doi.org/10.1080/00498254.2025.2498009","url":null,"abstract":"Rapamycin has been shown to be effective in the treatment of a variety of neurological disorders, including epilepsy. Intranasal drug administration is a novel mode of drug delivery that bypasses the blood-brain barrier and numerous biological effects thereby entering the central nervous system directly. Thus, the objective of this study was to investigate the brain entrance efficacy of rapamycin following intranasal administration of rapamycin.First, we found that acute high-dose administration with a total dose of 0.326 mg of rapamycin in a novel dosage form produced few side effects on body weight, various organs, and nasal mucosa in rats. Then, we examined the distribution of drug concentrations in the brain, nasal mucosa, and blood using the above dosage form administered intranasally to rats at 0.04 mg/kg. We found that intranasal administration was significantly more efficacious than oral administration for rapamycin brain delivery. We also discovered gender differences in drug absorption following intranasal administration of rapamycin, wherein rapamycin exhibited faster systemic absorption in female rats compared to males. Our study demonstrated that intranasal administration of rapamycin is highly effective and low toxic, which may provide a new delivery option for rapamycin therapy in brain diseases.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012979","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}

引用次数: 0