Biopharmaceutics & Drug Disposition最新文献

Ointment for Topical Ocular Delivery of Voriconazole: Formulation Development, In-Vitro Characterization & In-Vivo Pharmacokinetic Assessment. 局部眼给药伏立康唑软膏：配方开发、体外表征和体内药代动力学评估。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-04-16 DOI: 10.1002/bdd.70029

Amol Chhatrapati Bisen, Ayush Dubey, Sachin Nashik Sanap, Sristi Agrawal, Arpon Biswas, Rabi Sankar Bhatta

{"title":"Ointment for Topical Ocular Delivery of Voriconazole: Formulation Development, In-Vitro Characterization & In-Vivo Pharmacokinetic Assessment.","authors":"Amol Chhatrapati Bisen, Ayush Dubey, Sachin Nashik Sanap, Sristi Agrawal, Arpon Biswas, Rabi Sankar Bhatta","doi":"10.1002/bdd.70029","DOIUrl":"https://doi.org/10.1002/bdd.70029","url":null,"abstract":"Voriconazole (VCZ) is a broad-spectrum antifungal agent widely used for treating fungal infections caused by Candida, Aspergillus, and Fusarium species, which are commonly associated with fungal keratitis (FK). Topical ophthalmic ointments offer several advantages over conventional eye drops, including prolonged retention on the ocular surface, sustained drug release, and improved bioavailability. In this study, we formulated and optimized a VCZ-loaded ophthalmic ointment intended for effective management of FK. The ointments were prepared using emulsifying wax and varying proportions of liquid paraffins through the fusion method. Among all the formulations, batch F4 demonstrated optimal properties, including a stable, opaque white appearance with drug content of 103.7 ± 2.4%. Microscopic examination showed no drug crystallization, and differential scanning calorimetry (DSC) confirmed the absence of drug-excipient interactions. The in vitro release profile of F4 showed 70% drug release over 24 h, fitting the Higuchi kinetic model, indicative of a sustained release pattern. Ex vivo transcorneal studies revealed that 13.22 ± 0.81% of the drug permeated across the cornea, while 2.51 ± 0.03% remained entrapped in the corneal tissue after 24 h. Ocular irritation studies demonstrated the formulation was non-irritant and safe for ophthalmic use. Furthermore, in vivo pharmacokinetic evaluation in rabbits showed significantly higher corneal drug concentrations for F4 (Cmax: 400.76 ± 70.13 μg/mL) compared to a marketed formulation (Cmax: 32.60 ± 26.64 μg/mL), indicating approximately 12-fold enhanced retention. These findings suggest that the optimized ointment is a promising option for effective and prolonged ocular delivery of VCZ in the treatment of FK.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687948","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

Corneal Targeted Mucoadhesive Emulsion for Prolonged Delivery of Voriconazole: Formulation Evaluation and Pharmacokinetic Assessment. 角膜靶向黏附乳剂延长伏立康唑给药：配方评价和药代动力学评价。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-04-11 DOI: 10.1002/bdd.70028

Amol Chhatrapati Bisen, Saurabh Srivastava, Sachin Nashik Sanap, Anjali Mishra, Arpon Biswas, Sristi Agrawal, Rabi Sankar Bhatta

{"title":"Corneal Targeted Mucoadhesive Emulsion for Prolonged Delivery of Voriconazole: Formulation Evaluation and Pharmacokinetic Assessment.","authors":"Amol Chhatrapati Bisen, Saurabh Srivastava, Sachin Nashik Sanap, Anjali Mishra, Arpon Biswas, Sristi Agrawal, Rabi Sankar Bhatta","doi":"10.1002/bdd.70028","DOIUrl":"https://doi.org/10.1002/bdd.70028","url":null,"abstract":"Voriconazole, a broad-spectrum triazole antifungal, is widely prescribed for fungal keratitis (FK) caused by Candida, Aspergillus, and Fusarium species. Conventional ophthalmic solutions are limited by rapid clearance and low bioavailability. This study describes the development of a voriconazole-loaded ophthalmic emulsion to improve ocular residence and drug disposition. Emulsions were prepared with soybean oil and Tween 80 via high-shear homogenization, with batch VE-3 exhibiting favorable properties, including nanosized globules (95.8 ± 50.2 nm, PDI 0.197), pH 6.94 ± 0.14, high drug content (104.55% ± 7.9%), and physicochemical stability. DSC confirmed the absence of drug-excipient interactions, whereas osmolality (280 ± 4 mOsm/L) and conductance (77.59 ± 1.7 S/m) demonstrated ocular compatibility. To enhance mucoadhesion and prolong corneal residence, chitosan was incorporated into VE-3, yielding CS-VE-3. In vitro release studies showed 81% drug release from VE-3 versus 65% from CS-VE-3, with the latter following Higuchi kinetics, consistent with sustained release. Ex vivo transcorneal studies revealed comparable permeation for VE-3 (43.2% ± 1.14%) and CS-VE-3 (47% ± 1.22%), but distinct drug retention profiles (11.41% ± 0.73% vs. 5.09% ± 0.30%). In vivo pharmacokinetic assessment demonstrated Cmax values of 9.66 ± 3.49 μg/mL (marketed), 10.47 ± 6.43 μg/mL (VE-3), and a four-folds higher 41.67 ± 28.48 μg/mL for CS-VE-3, indicating prolonged corneal contact with chitosan incorporation. Ocular irritation studies confirmed safety and tolerability. The optimized mucoadhesive emulsion offers a promising strategy for sustained ocular delivery of voriconazole, potentially improving therapeutic outcomes in FK management.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662062","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

A Novel Slowly Self-Emulsifying Drug Delivery System: Prolonged Systemic Exposure of Tacrolimus With Reduced Risks of Systemic Side Effects. 一种新型缓慢自乳化给药系统：他克莫司长期全身暴露，降低全身副作用的风险。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-04-10 DOI: 10.1002/bdd.70030

Kohei Yamada, Keiya Sonobe, Akihisa Miura, Toshinobu Suzuki, Hiroyuki Uchida, Masataka Katsuma, Hideyuki Sato, Satomi Onoue

{"title":"A Novel Slowly Self-Emulsifying Drug Delivery System: Prolonged Systemic Exposure of Tacrolimus With Reduced Risks of Systemic Side Effects.","authors":"Kohei Yamada, Keiya Sonobe, Akihisa Miura, Toshinobu Suzuki, Hiroyuki Uchida, Masataka Katsuma, Hideyuki Sato, Satomi Onoue","doi":"10.1002/bdd.70030","DOIUrl":"https://doi.org/10.1002/bdd.70030","url":null,"abstract":"This study aimed to design and characterize a new type of self-emulsifying drug delivery system (SEDDS), slowly SEDDS (SL-SEDDS), for long-lasting systemic exposure of tacrolimus (TAC) with reduced nephrotoxicity. TAC-loaded SL-SEDDS (SL-SEDDS/TAC) was prepared by semi-solidifying TAC-loaded SEDDS (SEDDS/TAC) composed of Capryol 90, Cremophor EL, and polyethylene glycol 400 with Geleol. SEDDS samples were evaluated regarding physicochemical and biopharmaceutical properties. Both SEDDS/TAC and SL-SEDDS/TAC formed fine emulsions in water. The dissolution of SEDDS/TAC reached approximately 100% within the initial 30 min in simulated gastric fluid (SGF), and the SL-SEDDS/TAC samples exhibited slower dissolution than SEDDS/TAC in a Geleol content-dependent manner. SL-SEDDS/TAC with a Geleol content of 17.5 wt% showed 25% dissolution in SGF for 2 h, followed by an additional 31% dissolution in simulated intestinal fluid for 10 h. The sample was selected as a favorable SL-SEDDS/TAC for further studies because of its slow and continuous dissolution. Oral SEDDS/TAC and the selected SL-SEDDS/TAC (10 mg-TAC/kg) offered almost identical bioavailability of 18% and 19%, respectively, in rats. Compared with SEDDS/TAC, SL-SEDDS/TAC achieved a 32% decrease in the maximum plasma concentration, a risk factor of nephrotoxicity, from 383 to 262 ng/mL with significantly prolonged mean residence time. In a rat model of acute kidney injury, SL-SEDDS/TAC (10 mg-TAC/kg/day, 3 days) attenuated the elevation of blood nitrogen urea by 33% compared to SEDDS/TAC, suggesting a reduction in nephrotoxic risks. SL-SEDDS could be a promising dosage form to control oral absorption of TAC for effective and safe medication.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653635","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

Improvement of XZP8257 Dissolution Properties Through Amorphous and Mixed-Phase Precipitate Formation in Biorelevant Media. 通过形成非晶相和混合相沉淀改善XZP8257在生物相关介质中的溶解性能

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-04-07 DOI: 10.1002/bdd.70025

Miao Zhang, Shudong Zhang, Bin Wu, Zhe Zhang, Qin Hu, Lin Wang, Dongyang Liu

{"title":"Improvement of XZP8257 Dissolution Properties Through Amorphous and Mixed-Phase Precipitate Formation in Biorelevant Media.","authors":"Miao Zhang, Shudong Zhang, Bin Wu, Zhe Zhang, Qin Hu, Lin Wang, Dongyang Liu","doi":"10.1002/bdd.70025","DOIUrl":"https://doi.org/10.1002/bdd.70025","url":null,"abstract":"Although precipitation of poorly soluble drugs in the gastrointestinal (GI) tract is often considered detrimental to bioavailability, the solid-state nature of the precipitate, either crystalline or amorphous, may critically redefine its impact. Contrasting with reported crystalline precipitates of weakly basic drugs, this study investigates XZP8257 (C27H23Cl2N3O4S), a poorly soluble weakly acidic/zwitterionic compound (BCS II), to explore how GI fluid composition governs precipitate formation and its resulting physicochemical properties. Precipitates were generated in simulated intestinal media with varied bile salt concentrations and pH values. Their solid-state forms were characterized using XRD, SEM, FTIR, and DSC, whereas dissolution performance was evaluated via equilibrium solubility and intrinsic dissolution rate (IDR) measurements. Elevated bile salt concentrations induced a molecular structural transition in XZP8257 and facilitated the formation of crystalline-amorphous mixed precipitates, a phenomenon distinct from the crystalline precipitates typically reported. These novel precipitates exhibited a 5.29- to 22.1-fold increase in equilibrium solubility and a 0.7- to 2.35-fold improvement in IDR compared to the crystalline API. This study reveals that for weakly acidic compounds like XZP8257, precipitate formation in the GI tract can lead to high energy, readily redissolving solid forms, potentially enhancing rather than limiting absorption. This challenges the uniform negative view of precipitation and underscores the necessity of compound-specific precipitate characterization to accurately predict oral absorption, especially in physiologically based biopharmaceutics models.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627145","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

Cyclooxygenase-2 Inhibition and Anti-Platelet Aggregation Activity of Astaxanthin-Hydrogel in Comparison to Celecoxib Against Rheumatoid Arthritis in Wistar Rat Model. 虾青素-水凝胶与塞来昔布对Wistar大鼠类风湿关节炎的抑制作用及抗血小板聚集活性比较

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-24 DOI: 10.1002/bdd.70027

Anzeela Ghaffar, Sumaira Sharif, Quindeel Naveed, Taimoor Aslam, Madeeha Shahzad Lodhi, Iffat Nayila

{"title":"Cyclooxygenase-2 Inhibition and Anti-Platelet Aggregation Activity of Astaxanthin-Hydrogel in Comparison to Celecoxib Against Rheumatoid Arthritis in Wistar Rat Model.","authors":"Anzeela Ghaffar, Sumaira Sharif, Quindeel Naveed, Taimoor Aslam, Madeeha Shahzad Lodhi, Iffat Nayila","doi":"10.1002/bdd.70027","DOIUrl":"https://doi.org/10.1002/bdd.70027","url":null,"abstract":"Rheumatoid arthritis is an auto-immune disease, commonly treated with celecoxib (Cyclooxygenase-2 inhibitor), which comes with serious cardiovascular threats. Astaxanthin is a natural carotenoid, possessing extraordinary anti-inflammatory and anti-platelet aggregation qualities. The aim of this study was to investigate the superlative effects of astaxanthin-hydrogel to inhibiting the cyclooxygenase-2 in comparison to celecoxib and its cardiac side-effects, specifically platelet aggregation. Induction of rheumatoid arthritis was accomplished by type-II-collagen/Complete Freund's adjuvant followed by a booster dose of Incomplete Freund's adjuvant and confirmed by arthritic score calculation, CRP and ACCPA tests. Astaxanthin-hydrogel was subcutaneously injected into the neck and back of arthritic Wistar rats in comparison to oral-celecoxib. Cyclooxygenase-2 inhibitory activity was observed by rat ELISA kit and platelet aggregation was monitored by optical chrono-log aggregometer. Results were compared by statistical analysis, executed through IBMM SPSS. The anti-inflammatory activity of 20 mg/week astaxanthin-hydrogel to inhibiting the cyclooxygenase-2 for 6 weeks in arthritic wistar rats was found more effective in comparison to 20 mg/day celecoxib. Continued use of 40 mg/day celecoxib for 8 weeks has been seen involved with platelet aggregation, whereas the regimen consisting of 20 mg/week astaxanthin-hydrogel administered with 20 mg/d celecoxib for 8 weeks was observed with no platelet aggregation. Celecoxib monotherapy was found associated with a little risk of platelet aggregation, whereas along with astaxanthin-hydrogel, no platelet aggregation was found. Notably, astaxanthin-hydrogel was significant to suppress the cyclooxygenase-2 in comparison to celecoxib.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282209","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

Ampicillin Is a Substrate of Organic Anion Transporters 3. 氨苄西林是有机阴离子转运体的底物

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-19 DOI: 10.1002/bdd.70024

Yu-Ting Liu, Xue-Yan Gou, Lu Gan, Yi-Mai MaLiu, Yan-Rong Ma, Xin-An Wu

引用次数: 0

Comparative Study on Cannabidiol-Loaded Solubilizing Systems for Improvement of Oral Bioavailability: Liposome and Cyclodextrin-Based Formulations. 负载大麻二酚的增溶系统改善口服生物利用度的比较研究：脂质体和环糊精为基础的配方。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-01 Epub Date: 2025-12-27 DOI: 10.1002/bdd.70019

Hideyuki Sato, Kenta Watanabe, Ryuji Yagi, Akifumi Yagi, Shingo Rikimura, Yoshitaka Shimizu, Kohei Yamada, Satomi Onoue

{"title":"Comparative Study on Cannabidiol-Loaded Solubilizing Systems for Improvement of Oral Bioavailability: Liposome and Cyclodextrin-Based Formulations.","authors":"Hideyuki Sato, Kenta Watanabe, Ryuji Yagi, Akifumi Yagi, Shingo Rikimura, Yoshitaka Shimizu, Kohei Yamada, Satomi Onoue","doi":"10.1002/bdd.70019","DOIUrl":"10.1002/bdd.70019","url":null,"abstract":"This study aimed to develop a CBD-loaded liposomal formulation (LIP/CBD) to improve its physicochemical properties and oral bioavailability (BA). LIP/CBD was prepared by the conventional solvent injection method. The physicochemical and pharmacokinetic properties of CBD were evaluated to clarify the possible improvement in the biopharmaceutical properties of CBD by the application of a liposomal system. For comparison, a cyclodextrin-based CBD formulation (CD/CBD) was prepared as a conventional solubilization system. Uniform spherical liposomes of LIP/CBD were observed by transmission electron microscopy, and the mean particle size was calculated to be approximately 120 nm with a polydispersity index of 0.13 and a zeta potential of -68 mV. The amount of CBD dissolved from crystalline CBD was very low under simulated intestinal pH condition (pH 6.8) due to its poor solubility and dispersibility. In contrast, LIP/CBD significantly enhanced the dissolution of CBD, as evidenced by 8-fold higher dissolution amount than that of crystalline CBD. Oral absorption of CBD from crystalline CBD was very poor owing to its low water solubility and severe first-pass metabolism. Orally administered LIP/CBD and CD/CBD exhibited significant improvements of oral absorption with 22- and 5.3-fold higher systemic exposure, respectively. The Tmax of LIP/CBD was longer than that of CD/CBD, possibly due to the contribution of lymphatic absorption enhanced by lipidic components. The application of a liposomal system to CBD could be a viable option to enhance the physicochemical properties and oral BA of CBD.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"3-11"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846312","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

Vector-Based Comparison and Average Slope Can Refine Bioequivalence Claims: A Machine and Deep Learning Approach. 基于向量的比较和平均斜率可以改进生物等效性声明：一种机器和深度学习方法。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-01 Epub Date: 2026-02-13 DOI: 10.1002/bdd.70023

Maria Kokkali, Vangelis D Karalis

引用次数: 0

Nose to Brain Delivery of Curcumin Loaded Therapeutic Nanostructures for Neurodegenerative Diseases. 神经退行性疾病中姜黄素负载治疗性纳米结构的鼻到脑递送。

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1002/bdd.70021

Rupsikha Kalita, Anupam Sarma, Himakshi Baruah, Asifa Zaman, Deepjyoti Goswami

{"title":"Nose to Brain Delivery of Curcumin Loaded Therapeutic Nanostructures for Neurodegenerative Diseases.","authors":"Rupsikha Kalita, Anupam Sarma, Himakshi Baruah, Asifa Zaman, Deepjyoti Goswami","doi":"10.1002/bdd.70021","DOIUrl":"10.1002/bdd.70021","url":null,"abstract":"Neurodegenerative diseases are progressive disorders that damage and eventually kill neurons in the central nervous system (CNS). In recent years, various research has been done on reliable and effective treatment methods for the most common neurodegenerative diseases such as Parkinson's, Alzheimer, and Migraine diseases. Different neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic, Lewy body disease can be treated by curcumin, which is a strong antioxidant polyphenol with neuroprotective and anti-amyloid properties. However, Blood-brain barrier (BBB) and blood cerebrospinal fluid barrier restricts the permeation of curcumin to the brain leads poor distribution of the drug in brain tissue. The intranasal pathway holds promise for enhancing the treatment of CNS disorders since it bypasses the BBB and increases the brain bioavailability of drug. As nanotechnology continues to improve, research on the delivery of drug through intranasal route has grown significantly in last 10 years. Several nanocarriers have been developed such as nano-emulsions, microspheres, dendrimers, liposomes, carbon-based nanoformulation, and nanoparticles to deliver curcumin to the brain via intranasal route for the treatment of neurodegenerative diseases. This study provided a thorough analysis of several curcumin nano-formulations used in intranasal pathway as a novel treatment for neurodegenerative diseases.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"12-36"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892090","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

Pharmacokinetic Studies of a Novel c-Met Targeting PROTAC Drug Candidate Using UPLC-MS/MS Quantification Methods. 基于UPLC-MS/MS定量方法的新型c-Met靶向PROTAC候选药物的药动学研究

IF 2 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2026-02-01 Epub Date: 2026-01-14 DOI: 10.1002/bdd.70022

Yan Gao, Xinyu Li, Chao Xin, Xiangdong Su, Lianfeng Ai, Jiangmeng Zeng, Shilin Liu, Jinxu Wang

{"title":"Pharmacokinetic Studies of a Novel c-Met Targeting PROTAC Drug Candidate Using UPLC-MS/MS Quantification Methods.","authors":"Yan Gao, Xinyu Li, Chao Xin, Xiangdong Su, Lianfeng Ai, Jiangmeng Zeng, Shilin Liu, Jinxu Wang","doi":"10.1002/bdd.70022","DOIUrl":"10.1002/bdd.70022","url":null,"abstract":"TPD354 is a novel Proteolysis Targeting Chimera (PROTAC) drug candidate that targets the degradation of cellular mesenchymal-epithelial transforming factor (c-Met) kinase. It showed significant therapeutic efficacy in vivo gastric cancer models. We have developed a robust and sensitive analytical method for evaluating the pharmacokinetic properties of TPD354, using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) to quantify drug concentrations in diverse biological matrices. The method was validated and applied to pharmacokinetic studies of the compound. The method exhibited excellent specificity in the linear range of 6.995-6995.000 ng/mL. Moreover, the method met or exceeded established criteria for precision, accuracy, recovery, and matrix effects, ensuring its suitability for in vivo analysis. The method was applied to the study of drug pharmacokinetics in rats, stability in different types of liver microsomes, and protein binding in plasma of different species. Our studies have demonstrated that TPD354 exhibits metabolic stability in liver microsomes and is characterized by high plasma protein binding, with a half-life of approximately 16 h in rats. These findings suggest that TPD354 is a promising PROTAC drug candidate, with strong potential for the treatment of c-Met targeted cancer.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"37-48"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984381","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