Biopharmaceutics & Drug Disposition最新文献

Integration of Data-Driven Techniques in Nanomedicines to Address Diagnosis and Drug Delivery Strategy for Therapy. 数据驱动技术在纳米医学中的集成，以解决诊断和药物递送策略的治疗。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-09-16 DOI: 10.1002/bdd.70016

Koyeli Girigoswami, Agnishwar Girigoswami

{"title":"Integration of Data-Driven Techniques in Nanomedicines to Address Diagnosis and Drug Delivery Strategy for Therapy.","authors":"Koyeli Girigoswami, Agnishwar Girigoswami","doi":"10.1002/bdd.70016","DOIUrl":"https://doi.org/10.1002/bdd.70016","url":null,"abstract":"The progress of drug designing, drug delivery systems (DDS), and disease diagnostic systems has significantly advanced pharmaceutical development, as evidenced by the FDA-approved nanomedicines with enhanced selectivity, controlled release, and synergistic therapeutic effects. However, the design and large-scale development of nanomaterial-based DDS remain challenging due to difficulties in managing and analyzing complex experimental data. The integration of data-driven techniques, high-throughput experimental networks and protocols, automation, artificial intelligence (AI), and machine learning (ML)-a framework known as the fourth paradigm of scientific research that offers a promising solution. This review article highlights milestones in applying these technologies to biomarker-based diagnosis and DDS, including nanomaterial design, and explores their potential to accelerate drug development and clinical translation. It also outlines the future prospects or directions for leveraging these approaches to create highly efficient, customizable nanomedicines and smart materials with defined physicochemical properties, aiming to benefit researchers in materials science, nanotechnology, and biomedical DDS development.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074393","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

Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule. 高脂肪膳食和最佳给药计划提高Vatiquinone的生物利用度。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-09-16 DOI: 10.1002/bdd.70015

Lucy Lee, Katsuyuki Murase, Martin Thoolen, Peter Giannousis, Diksha Kaushik, Lee Golden, Ronald Kong

{"title":"Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule.","authors":"Lucy Lee, Katsuyuki Murase, Martin Thoolen, Peter Giannousis, Diksha Kaushik, Lee Golden, Ronald Kong","doi":"10.1002/bdd.70015","DOIUrl":"https://doi.org/10.1002/bdd.70015","url":null,"abstract":"Vatiquinone, a 15-lipoxygenase (LO) inhibitor, is an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulation of energy metabolism. This investigation discusses the results of the food effect and three times a day (TID) dosing schedule studies data. The food effect study showed that absorption is significantly enhanced when vatiquinone was administered with fatty meals, either solid or liquid. Mean vatiquinone area under the concentration-time curve (AUC) values were 22-fold and 3-fold higher in subjects who consumed fatty meals and liquid meals, respectively, compared with subjects who fasted. With fatty meals, the intersubject variabilities appeared lower for AUC. The TID dosing study showed that the typical individual pharmacokinetic concentration profile exhibited 3 peaks on both Day 1 and after multiple dosing on Day 6. Vatiquinone exposures, AUC, and maximum concentration (Cmax) appeared to increase from 200 to 400 mg in a dose-proportional manner with moderate variabilities, ranging from approximately 35% to 65%. The mean Day 6 accumulation ratio (ARAUC) suggested an accumulation ratio of 1.61 and 1.73 for 200 and 400 mg, respectively. The results of both studies support the recommendation of administering vatiquinone TID with fatty meals taken on a convenient dosing regimen.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069033","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

The Role of Nasal Drug Delivery in Migraine Management and Brain-Targeted Therapy: Insights From Taiwan 鼻给药在偏头痛治疗和脑靶向治疗中的作用：来自台湾的见解。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-08-25 DOI: 10.1002/bdd.70013

Lien-Chung Wei, Hsien-Jane Chiu

引用次数: 0

Contribution of Organic Anion Transporter 3 in Delayed Elimination of Methotrexate by Concomitant Administration of Febuxostat 有机阴离子转运体3在非布司他联用延迟消除甲氨蝶呤中的作用。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-08-25 DOI: 10.1002/bdd.70014

Kenji Ikemura, Sakura Kobayashi, Danni Wang, Masahiro Okuda

{"title":"Contribution of Organic Anion Transporter 3 in Delayed Elimination of Methotrexate by Concomitant Administration of Febuxostat","authors":"Kenji Ikemura, Sakura Kobayashi, Danni Wang, Masahiro Okuda","doi":"10.1002/bdd.70014","DOIUrl":"10.1002/bdd.70014","url":null,"abstract":"Methotrexate is an antifolate agent used for the treatment of various malignancies and is mainly secreted via human organic anion transporter 3 (hOAT3) in the proximal tubular cells. Coadministration of the xanthine oxidase inhibitor, febuxostat, in patients receiving methotrexate has been reported to be associated with an elevated risk of hematological toxicity and increased plasma methotrexate levels. Because febuxostat has an inhibitory effect against hOAT3, it may inhibit renal elimination of methotrexate via hOAT3. However, the drug interaction between methotrexate and febuxostat via hOAT3 remains to be clarified. In the present study, we investigated the effect of febuxostat on pharmacokinetics of methotrexate in rats and drug interaction between methotrexate and febuxostat using hOAT3-expressing cultured cells. In the pharmacokinetics study using rats, concomitant administration of febuxostat significantly increased plasma concentration of methotrexate and prolonged its half-life. In vitro studies showed that febuxostat inhibited hOAT3-mediated transport of methotrexate in a concentration-dependent manner. Dixon plot indicated that inhibitory constant value of febuxostat against methotrexate transport via hOAT3 was 0.63 ± 0.01 μM. Moreover, the inhibitory effect of febuxostat was of noncompetitive type. Taken together, these results suggest that concomitant administration of febuxostat delayed elimination of methotrexate, at least in part, by noncompetitive inhibition of hOAT3-mediated methotrexate transport at clinical concentrations. The findings of this study provide novel information on drug interactions associated with febuxostat.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 4","pages":"165-171"},"PeriodicalIF":2.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdd.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940733","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}

引用次数: 0

The Effect of α-Mangostin on the Pharmacokinetic Profile of Tofacitinib in Rats Both In Vitro and In Vivo α-山竹苷对托法替尼体内体外大鼠药动学的影响。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-08-16 DOI: 10.1002/bdd.70012

Jiange Yao, Zebei Lu, Quan Zhou, Abdullah Al Mamun, Yaru Shi, Shuanghu Wang, Ying Yao

{"title":"The Effect of α-Mangostin on the Pharmacokinetic Profile of Tofacitinib in Rats Both In Vitro and In Vivo","authors":"Jiange Yao, Zebei Lu, Quan Zhou, Abdullah Al Mamun, Yaru Shi, Shuanghu Wang, Ying Yao","doi":"10.1002/bdd.70012","DOIUrl":"10.1002/bdd.70012","url":null,"abstract":"This study investigated the effects of α-mangostin (α-MG) on the pharmacokinetics of tofacitinib in vitro and in vivo, aiming to recommend its appropriate application in clinical practice. To investigate the values of IC50 and inhibition of α-MG in vitro, rat liver microsomes were incubated with tofacitinib. In this study, Sprague–Dawley rats were randomly assigned to three groups: a control group, a single-dose group (50 mg/kg of α-MG), and a multiple-dose group (50 mg/(kg/d) of α-MG for 7 days). Tofacitinib (10 mg/kg) was administered 30 min after the intervention of α-MG to each group. The plasma was collected from the caudal vein at different time points and in heparinized tubes. Tofacitinib metabolites in the plasma were determined by UPLC-MS/MS. Further analyses were conducted utilizing Pymol molecular docking simulation to evaluate the effect of α-MG on tofacitinib. Our results showed that MG inhibited the metabolism of tofacitinib in vitro by exhibiting both competitive and noncompetitive inhibition. More importantly, we found that multiple-dose administration of α-MG significantly increased the AUC(0–12h), AUC(0–∞), and Cmax, prolonged the t1/2 and shortened the MRT(0–12h) and MRT(0–∞) of tofacitinib. At the same time, the CLz/F was decreased, which was consistent with the results of in vitro experiments. Furthermore, we observed no significant difference between single-dose and multiple-dose groups. Intriguingly, α-MG and tofacitinib were close at the CYP3A4 spatial location. In summary, our investigation demonstrated that α-MG significantly impacts the metabolism of tofacitinib both in vitro and in vivo, suggesting potential herb–drug interactions (HDIs). The use of tofacitinib with herbs containing MG should be monitored clinically.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 4","pages":"155-162"},"PeriodicalIF":2.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdd.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862096","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}

引用次数: 0

Pharmacokinetic Study of Cefditoren Pivoxil in Breast Milk and Blood of Lactating Women 头孢地托林酯在哺乳期妇女母乳和血液中的药动学研究。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-08-12 DOI: 10.1002/bdd.70011

Zhuo Chen, Shiyin Feng, Linrui Cai, Dan Du, Qin Yu, Xianfeng Peng, Chunfeng Du, Qin Zou, Weiyi Guo, Fengshan Li

{"title":"Pharmacokinetic Study of Cefditoren Pivoxil in Breast Milk and Blood of Lactating Women","authors":"Zhuo Chen, Shiyin Feng, Linrui Cai, Dan Du, Qin Yu, Xianfeng Peng, Chunfeng Du, Qin Zou, Weiyi Guo, Fengshan Li","doi":"10.1002/bdd.70011","DOIUrl":"10.1002/bdd.70011","url":null,"abstract":"<div>\u0000 \u0000 To provide a theoretical basis for the rational use of cefditoren pivoxil in lactating women by conducting a pharmacokinetic study of cefditoren in the blood and milk of these women. Twelve participants meeting the inclusion criteria took cefditoren pivoxil tablets 200 mg after a meal, and the breast milk was collected over certain time periods with their volumes recorded. Blood samples were also collected at certain time points for pharmacokinetic analysis. Conduct a statistical analysis on the drug concentrations in breast milk and plasma and their correlation. Assessing the risk of taking cefditoren pivoxil during lactation using the milk-to-plasma ratio (M/P) and the relative infant dose (RID). Adverse events were monitored throughout the study period. Twelve lactating women participated in the study, providing a total of 84 breast milk samples. The correlation coefficient between cefditoren in breast milk and cefditoren in maternal plasma is 0.748 and is significant at the 0.01 level, with an M/P ratio of 0.008, and a RID of 0.0073%. Cefditoren is minimally distributed in human breast milk. There is a significant positive correlation between maternal blood drug levels and milk drug levels. Based on the M/P ratio and RID, it is inferred that the infant’s exposure is low, that is, the absolute dose of cefditoren transmitted to the infant through breastfeeding is low and is unlikely to cause any significant adverse effects. The results of this study will provide information for the use of cefditoren pivoxil in lactating women.\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 4","pages":"147-154"},"PeriodicalIF":2.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833893","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

Multifaceted Evaluation of Nano Encapsulated Polymeric Scopoletin Against HT-29 Colon Cancer Cells 纳米包封聚合东莨菪素抗HT-29结肠癌细胞的多方面研究。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-08-06 DOI: 10.1002/bdd.70010

Kunnathur Murugesan Sakthivel, Rajan Radha Rasmi, Kalavathy Murugan Kumar, Kavitha Thangavelu, Loganathan Chandramani Priya Dharshini, Anitha Nagarajan, Balasubramanian Ramesh

{"title":"Multifaceted Evaluation of Nano Encapsulated Polymeric Scopoletin Against HT-29 Colon Cancer Cells","authors":"Kunnathur Murugesan Sakthivel, Rajan Radha Rasmi, Kalavathy Murugan Kumar, Kavitha Thangavelu, Loganathan Chandramani Priya Dharshini, Anitha Nagarajan, Balasubramanian Ramesh","doi":"10.1002/bdd.70010","DOIUrl":"10.1002/bdd.70010","url":null,"abstract":"<div>\u0000 \u0000 In the sphere of medical research, nanoencapsulated polymeric drugs in biological circumstances are an intriguing issue for therapeutical diagnosis. The nanoprecipitation approach was employed in this study to synthesis the nanoencapsulated polymeric scopoletin (NEP-Sc) and tested its effect against the HT-29 cell line (human colorectal adenocarcinoma cells). Further, the synthesized NEP-Sc was then characterized by ultra-visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray analysis (EDAX), and dynamic light scattering (DLS) analysis. All the analysis confirmed the effective synthesis of NEP-Sc. The synthesized NEP-Sc was validated as anticancer drug through the conventional MTT assay, neutral red uptake assay, apoptosis assay using AO/EB and lactate dehydrogenase assay and trypan blue assay against HT-29 cells. The docking studies of scopoletin with multiple genes were also carried out using the PyRx—virtual screening tool. The findings indicated that increase in concentration of NEP-Sc exhibited dose dependent action of cell death against the HT-29 colon cancer cells. To summarize, the observed results of anticancer and computational modeling studies underscores the therapeutic potential of NEP-Sc in treating colon cancer.\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 3","pages":"127-144"},"PeriodicalIF":2.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788173","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

Effect of Curcuminoids on Pharmacokinetics and Pharmacodynamics of Atorvastatin in Hyperlipidemia Rats and Its Potential Mechanism 姜黄素对高脂血症大鼠阿托伐他汀药动学和药效学的影响及其可能机制。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-07-30 DOI: 10.1002/bdd.70009

Jiao Li, Jinzhen Wang, Benlu Zhong, Fan Wu, Weihong Yin, Siwen Wang, Xueying Yan, Mingyu Cui

{"title":"Effect of Curcuminoids on Pharmacokinetics and Pharmacodynamics of Atorvastatin in Hyperlipidemia Rats and Its Potential Mechanism","authors":"Jiao Li, Jinzhen Wang, Benlu Zhong, Fan Wu, Weihong Yin, Siwen Wang, Xueying Yan, Mingyu Cui","doi":"10.1002/bdd.70009","DOIUrl":"10.1002/bdd.70009","url":null,"abstract":"<div>\u0000 \u0000 Curcuminoids (CURs), natural polyphenols, are often combined with atorvastatin to treat hyperlipidemia. In order to assess the safety of combination, the effect of CURs on Cytochrome P450 (CYP) 3A2 activity in rats was investigated. Additionally, the effect of CURs on pharmacokinetics and pharmacodynamics of atorvastatin in rats was evaluated. The effect of CURs on CYP3A2 activity was studied using the probe drug method (dapsone as a probe drug). Pharmacokinetic parameters of atorvastatin with or without CURs were calculated to evaluate herb-drug interactions (HDIs). The effect of CURs on pharmacodynamics of atorvastatin was investigated by blood lipid, oxidative stress, aminotransferases, inflammatory factors and liver histopathology. Cmax, AUC, and t1/2 of dapsone in CURs group significantly increased (p < 0.05). Cmax, AUC, and t1/2 of atorvastatin in combination group significantly increased both in normal and hyperlipidemia rats (p < 0.01). Pharmacodynamics indexes of all treatment groups were significantly improved. There was no significant difference between AC group and combination group except HDL-C, SOD and liver index. In conclusion, CURs combined with atorvastatin could not effectively enhance the lipid-lowering effect or alleviate liver damage. However, CURs could inhibit CYP3A2 activity in rats and increase plasma exposure of atorvastatin, which might increase the risk of HDIs. The findings provided new insight into the combination of CURs and atorvastatin in treating hyperlipidemia.\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 3","pages":"112-126"},"PeriodicalIF":2.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752233","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 Mechanism of Ketamine-Apatinib by CYP2C9 and 3A4: A Prediction of Possible Drug-Drug Interaction 氯胺酮-阿帕替尼对CYP2C9和3A4的抑制机制：可能的药物-药物相互作用的预测。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-05-21 DOI: 10.1002/bdd.70008

Xiang Zheng, Haiyan Chen, Dan Lin, Guo-Xin Hu, Hongyu Zhou

{"title":"Inhibition Mechanism of Ketamine-Apatinib by CYP2C9 and 3A4: A Prediction of Possible Drug-Drug Interaction","authors":"Xiang Zheng, Haiyan Chen, Dan Lin, Guo-Xin Hu, Hongyu Zhou","doi":"10.1002/bdd.70008","DOIUrl":"10.1002/bdd.70008","url":null,"abstract":"<div>\u0000 \u0000 Most cancer patients experience severe pain, and apatinib, a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, demonstrates therapeutic efficacy against gastric cancer. Ketamine, a psychotropic drug used for cancer pain relief, exhibits potential in inhibiting gastric cancer progression but is associated with dose-dependent adverse effects including neurological toxicity and dependency. Thus, clarifying whether apatinib influences ketamine therapy when co-administered is critical. In this study, we investigated apatinib's inhibitory effects on ketamine metabolism using CYP2C9 and CYP3A4 isoform assays. Results showed that apatinib exerted inhibition of ketamine metabolism, acted as a noncompetitive inhibitor of CYP2C9*1, CYP2C9*16, and rat liver microsomes (RLM), a competitive inhibitor of CYP2C9*3 and CYP2C9*13, and a mixed-model inhibitor of four CYP3A4 alleles (*1, *4, *18, and *23). Molecular docking revealed apatinib's stronger binding affinity (−10.4 kcal/mol) to CYP3A4*1 than ketamine (−6.9 kcal/mol). Consequently, co-administration may increase adverse risk in poor metabolizers (PMs), warranting in vivo validation of their therapeutic interaction.\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 3","pages":"104-111"},"PeriodicalIF":2.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109597","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

Influences of Magnesium Isoglycyrrhizinate on the Pharmacokinetics of Almonertinib in Rats and Its Potential Mechanisms 异甘草酸镁对阿莫那替尼大鼠药动学的影响及其可能机制。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2025-05-07 DOI: 10.1002/bdd.70007

Yuhao Fu, Ying Li, Yajing Li, Xueru He, Xuejiao Xun, Zhanjun Dong

{"title":"Influences of Magnesium Isoglycyrrhizinate on the Pharmacokinetics of Almonertinib in Rats and Its Potential Mechanisms","authors":"Yuhao Fu, Ying Li, Yajing Li, Xueru He, Xuejiao Xun, Zhanjun Dong","doi":"10.1002/bdd.70007","DOIUrl":"10.1002/bdd.70007","url":null,"abstract":"<div>\u0000 \u0000 Almonertinib has been approved for the first-line therapy of advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). As a hepatoprotective agent, magnesium isoglycyrrhizinate (MgIG) was widely used in the treatment of drug-induced liver injury. Although Almonertinib is commonly prescribed in combination with MgIG in clinical application, the interaction research between them has not been reported. This research was conducted to explore the influences of MgIG on the pharmacokinetics of Almonertinib in rats and to investigate its possible molecular mechanisms. The plasma concentration of Almonertinib in male Sprague-Dawley (SD) rats was determined by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), the messenger RNA (mRNA) and protein expression levels of CYP3A1 (homologous to human CYP3A4) and P-glycoprotein (P-gp) in rat livers were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses. MgIG increased systemic exposure of Almonertinib significantly, resulting in increased AUC0−t, AUC0−∞, Cmax, and t1/2, and decreased CLz. Furthermore, MgIG can markedly down-regulate the expression levels of CYP3A1 and P-gp in rat livers. There is a drug–drug interaction (DDI) between MgIG and almonertinib, which leads to an increase of systemic exposure for almonertinib. Meanwhile, CYP3A1 and P-gp in the liver may be the primary targets of mediating the DDI, but further clinical trials are needed to confirm these results.\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 3","pages":"95-103"},"PeriodicalIF":2.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959346","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