{"title":"Species Differences in Carboxylesterases Among Humans, Cynomolgus Monkeys, and Mice in the Hydrolysis of Atorvastatin Derivatives.","authors":"Masato Takahashi, Sachiko Sakai, Kohei Takahashi, Masakiyo Hosokawa","doi":"10.1002/bdd.70003","DOIUrl":"https://doi.org/10.1002/bdd.70003","url":null,"abstract":"<p><p>Nonclinical trials are crucial for assessing pharmaceutical efficacy and safety prior to clinical trials. However, disparities in drug metabolism between humans and animals complicate extrapolating animal data to humans. Variability in drug-metabolizing enzymes, such as carboxylesterases (CESs), contributes to differences in drug kinetics. This study aimed to explore species disparities in CES substrate specificity among humans (hCES1), mice (mCES1), and cynomolgus monkeys (mfCES1) using diverse atorvastatin ester derivatives. This study measured hydrolysis rates of 30 atorvastatin derivatives. Metabolites were identified via HPLC with an internal standard, measuring rates per unit time and enzyme amount. Enzyme metabolic activity was compared using hydrolysis rates. The structure of the alkoxy group resulted in differences ranging from approximately half to 8.97-fold between hCES1 and mCES1 and differences ranging from similar to 15.82-fold between hCES1 and mfCES1. Caution is warranted when extrapolating animal data to humans, especially for esters with diverse structures. Our focus on the alkoxy group structure highlights its impact on hydrolysis rates. Further investigation into species differences among CES enzymes is essential for accurate translational research.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699209","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}
S. K. Mydhili, S. Nithyaselvakumari, K. Padmanaban, D. Karunkuzhali
{"title":"An Optimised Mobilenet V2 Attention Parallel Network for Predicting Drug–Drug Interactions Through Combining Local and Global Features","authors":"S. K. Mydhili, S. Nithyaselvakumari, K. Padmanaban, D. Karunkuzhali","doi":"10.1002/bdd.70001","DOIUrl":"10.1002/bdd.70001","url":null,"abstract":"<div><p>Drug–drug interactions (DDIs) are an important concern in the clinical practice and drug development process as these may lead to serious adverse effects on patient safety. Thorough DDI prediction is important for effective medication management and reduced risk factors. This work presents a new technique, namely MV2SAPCNNO: MobileNetV2 with simplicial attention network-based parallel convolutional neural network and narwhal optimiser, for improving the precision of DDI prediction. The proposed method starts with data preprocessing, including normalisation and noise reduction, to enhance the quality of the data. Then, MobileNetV2 with simplicial attention network (MV2SAN) is used to extract both local and global features from the dataset. These features are processed using a parallel convolutional neural network (PCNN), optimised by the narwhal optimiser (NO) to improve parameter tuning, minimise error and reduce computational complexity. The performance of the model is evaluated using accuracy, precision, recall and F-score. Experimental results prove that MV2SAPCN-NO achieves better performance over the current models of DDI prediction in accuracy and enhanced classification metrics. The narwhal optimiser enhances the model's convergence efficiency and decreases computational time with an excellent predictive performance. An efficient and accurate DDI prediction model was proposed called MV2SAPCNNO. This model actually outperformed traditional models, and such findings were exhibited to contribute towards secure medication administration, drug development processes and protection of patients in clinical practice.</p></div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 1","pages":"22-32"},"PeriodicalIF":1.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603838","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}
Valerio Taggi, Anima M. Schäfer, Stefan Oswald, Jonny Hanna Kinzi, Isabell Seibert, Alaa Al-Khatib, Henriette E. Meyer zu Schwabedissen
{"title":"Pregnenolone Sulfate Permeation at the Blood–Brain Barrier is Independent of OATP2B1—In Vivo and In Vitro Insights","authors":"Valerio Taggi, Anima M. Schäfer, Stefan Oswald, Jonny Hanna Kinzi, Isabell Seibert, Alaa Al-Khatib, Henriette E. Meyer zu Schwabedissen","doi":"10.1002/bdd.70002","DOIUrl":"10.1002/bdd.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Sulfated steroids such as pregnenolone sulfate (PregS) are important for neuronal development and cognitive functions. Given the hydrophilic sulfate moiety, it is assumed that PregS requires an active transport mechanism to cross the blood–brain barrier (BBB). The human organic anion transporting polypeptide (OATP)2B1 has been previously shown to transport sulfated steroids and is therefore a proposed candidate for the transport of PregS. In this study, we aimed to investigate the role of OATP2B1 in the uptake of PregS in the brain. Tritium-labeled PregS was intravenously administered to humanized (<i>SLCO2B1</i><sup><i>+/+</i></sup>), knockout (<i>rSlco2b1</i><sup><i>−/−</i></sup>), and wildtype (WT) rats. Accumulation of the radiotracer was analyzed in rat brain, liver, small intestine, kidney, heart, and muscle. Moreover, transporter expression in brain microvessels was assessed through targeted proteomics and Western blot analysis. The involvement of hOATP2B1 in PregS transport across the BBB was further studied using a hBMEC-based in vitro BBB model. Our results indicated no significant difference in accumulation of the radiotracer among the different rat genotypes in the brain or in other tissues. In line with what we observed in the rat model, the subsequent in vitro study showed no involvement of hOATP2B1 in the transport of PregS. Taken together, our findings highlight the species-specific differences in transporter expression and suggest that OATP2B1 does not mediate PregS uptake across the BBB.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 1","pages":"33-46"},"PeriodicalIF":1.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603839","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}
Xin Wang, Yangnan Chen, Yan Liu, Danqing Wu, Yanqiu Long, Shuangying Gui, Zhiyun Zheng, Ning He
{"title":"Nanostructured Lipid Carriers-Based Topical Gel of Betulinic Acid: In Vitro, In Vivo Evaluation and Dermatokinetic Analysis","authors":"Xin Wang, Yangnan Chen, Yan Liu, Danqing Wu, Yanqiu Long, Shuangying Gui, Zhiyun Zheng, Ning He","doi":"10.1002/bdd.70000","DOIUrl":"10.1002/bdd.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to improve the penetration of betulinic acid (BA) into skin efficiently by incorporating it into a nanostructured lipid carrier (NLC)-based gel. BA-NLC was prepared by the melt-emulsification and low-temperature solidification method. The optimized formulation was incorporated into the hydrogel and evaluated for pH, in vitro release, occlusion factor, and dermatokinetics. Furthermore, the transdermal penetration mechanism of the NLC gel was investigated by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), skin histological staining, and fluorescence microscopic methods. The optimized NLC showed a particle size of 153.40 nm and a high <i>EE</i> of 86.21%. In vitro drug release behavior of the BA-NLC gel showed higher cumulative release at 24 h (67.17 ± 2.39%) compared to the free drug (57.53 ± 2.17%). In vivo dermatokinetic studies disclosed that the BA-NLC gel presented elevated <i>C</i><sub>max</sub> and <i>AUC</i><sub>0–24</sub> in the epidermis and dermis in contrast to the conventional gel. FT-IR and DSC research indicated that the NLC formulations changed the configuration of skin keratin and augmented lipid fluidity, thus facilitating the percutaneous permeability of actives. Fluorescence microscopy also indicated improved skin penetration of the BA-NLC gel. Hence, the optimized NLC gel could potentially be a promising drug nanocarrier to boost skin drug penetration and retention.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 1","pages":"10-21"},"PeriodicalIF":1.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555788","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":"In Vivo Animal Spices and Experimental Technique to Evaluate Sustained Release Granules","authors":"Masateru Miyake, Mayumi Kano, Yuji Suzuki, Masami Kato, Tadashi Mukai","doi":"10.1002/bdd.2407","DOIUrl":"10.1002/bdd.2407","url":null,"abstract":"<div>\u0000 \u0000 <p>Establishment of a suitable animal model to evaluate sustained release (SR) formulations is very important because it reduces the development time of SR formulations. Beagle dogs are often used to evaluate prototype formulations since they can be directly administered powder, such as drug substance. However, the physiological condition of dogs is very different to that of humans. Therefore, the benefits of utilizing beagle dogs for the evaluation of modified release formulations such as sustained release formulations and enteric-coated formulations are doubtful. To clarify the best animal and/or experimental technique for the evaluation of modified release formulations, we investigated dipyridamole pharmacokinetics from prototype sustained release granules by utilizing beagle dogs, propantheline bromide-treated (PBT) beagle dogs, and miniature pigs. In normal dogs, the intestinal absorption and sustained release effect of dipyridamole decreased in the 20 mg sustained release granule. However, in PBT dogs, a sustained release effect was observed in the 45 mg sustained release granule, and its bioavailability was also maintained. Accordingly, PBT dogs could be the best to evaluate sustained release formulations such as tablets and granules, and the use of miniature pigs might be better to evaluate granules with equal to or less than 1 mm diameter.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"46 1","pages":"3-9"},"PeriodicalIF":1.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920586","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":"Application of Physiologically Based Pharmacokinetic Model to Compare the Biodistribution of Liposomal Amphotericin B With Conventional Amphotericin B Deoxycholate in Humans","authors":"Xueyuan Zhang, Yingying Yang, Manman Wang, Huanhuan Qi, Chunlei Li, Limei Zhao","doi":"10.1002/bdd.2406","DOIUrl":"10.1002/bdd.2406","url":null,"abstract":"<div>\u0000 \u0000 <p>Amphotericin B (AmB) has been a cornerstone in the treatment of invasive fungal infections for over 6 decades. Compared with conventional amphotericin B deoxycholate (AmB-DOC), liposomal amphotericin B has comparable efficacy but less nephrotoxicity. The main purpose of this study was to investigate the reason why liposomal amphotericin B has similar therapeutic effects but lower toxicity and the differences of distribution in humans between liposomal amphotericin B and AmB-DOC. To compare the distribution of liposomal amphotericin B and AmB-DOC in humans, the physiologically based pharmacokinetic (PBPK) model was established by bottom-up stepwise method. A rat PBPK model was established firstly, then verified in mouse level in consideration of interspecies differences in physiological- and drug-specific parameters, and finally the PBPK model was extrapolated to humans. Based on preclinical and clinical pharmacokinetic (PK) studies, the AmB-DOC and liposomal amphotericin B PBPK model were established, respectively. The simulated results of human PBPK model showed that the liposomal formulation changed the pharmacokinetic characteristics of AmB. Compared with AmB-DOC, the plasma exposure of liposomal formulation was higher, but the renal exposure was significantly reduced.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"45 4-6","pages":"208-219"},"PeriodicalIF":1.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891846","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":"Exploring the Potential of Nasal Drug Delivery for Brain Targeted Therapy: A Detailed Analysis","authors":"Maitrayee Ghosh, Debajyoti Roy, Shubham Thakur, Amrinder Singh","doi":"10.1002/bdd.2400","DOIUrl":"10.1002/bdd.2400","url":null,"abstract":"<div>\u0000 \u0000 <p>The brain is a sensitive organ with numerous essential functions and complex mechanisms. It is secluded and safeguarded from the external environment as part of the central nervous system (CNS), serving as a sanctuary. By regulating their selective and specific absorption, efflux, and metabolism in the brain, the CNS controls brain homeostasis and the transit of endogenous and foreign substances. The mechanism which protects the brain from environmental chemicals, also prevent the entry of therapeutic chemicals to it. The delivery of molecules to the brain is hindered by several major barriers, such as the blood–brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and blood-tumor barrier. BBB is formed by the combination of cerebral endothelial cells, astrocytes, neurons, pericytes and microglia. It is a tight junction of capillary endothelial cells, preventing the diffusion of solute into the brain. BCSFB is the second barrier, located at the choroid plexus, separating the blood from cerebrospinal fluid (CSF). It is comparatively more permeable than BBB. An uneven distribution of microvasculature across the tumor interstitial compromises drug delivery to neoplastic cells of a solid tumor, resulting in spatially inconsistent drug administration. Nasal drug delivery to the brain is a method of drug delivery that tries to deliver therapeutic substances directly from the nasal cavity to the central nervous system including the brain. In this review, besides the role of barriers we have discussed in detail about approaches adapted to deliver drugs to the brain along with mechanisms through nasal route. Further, different commercial formulations, clinical trials and patents have been thoroughly elaborated to date. The findings suggest that the nose-to-brain drug delivery method holds promise as an evolving approach, potentially contributing to the specific and targeted delivery of drugs into the brain.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"45 4-6","pages":"161-189"},"PeriodicalIF":1.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811719","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 limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients","authors":"Liangmo Lin, Mianhui Hong, Xiangjun Fu","doi":"10.1002/bdd.2399","DOIUrl":"10.1002/bdd.2399","url":null,"abstract":"<p>Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC<sub>0–12</sub> in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC<sub>0–12</sub> using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC<sub>0–12</sub> (<i>r</i><sup>2</sup> < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC<sub>0–12</sub> (<i>r</i><sup>2</sup> > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC<sub>0–12</sub>. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC<sub>0–12</sub> with precise results and minimal bias.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"45 4-6","pages":"201-207"},"PeriodicalIF":1.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340466","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}
Hyo-jeong Ryu, Seongsung Kwak, Misun Park, Hwi-yeol Yun
{"title":"Model-based interspecies interpretation of botulinum neurotoxin type A on muscle-contraction inhibition","authors":"Hyo-jeong Ryu, Seongsung Kwak, Misun Park, Hwi-yeol Yun","doi":"10.1002/bdd.2398","DOIUrl":"10.1002/bdd.2398","url":null,"abstract":"<p>Botulinum neurotoxins (BoNTs) are commonly used in therapeutic and cosmetic applications. One such neurotoxin, BoNT type A (BoNT/A), has been studied widely for its effects on muscle function and contraction. Despite the importance of BoNT/A products, determining the blood concentrations of these toxins can be challenging. To address this, researchers have focused on pharmacodynamic (PD) markers, including compound muscle action potential (CMAP) and digit abduction scoring (DAS). In this study, we aimed to develop a probabilistic kinetic-pharmacodynamic (K-PD) model to interpret CMAP and DAS data obtained from mice and rats during the development of BoNT/A products. The researchers also wanted to gain a better understanding of how the estimated parameters from the model relate to the bridging of animal models to human responses. We used female Institute of Cancer Research mice and Sprague-Dawley (SD) rats to measure CMAP and DAS levels over 32 weeks after administering BoNT/A. We developed a muscle-contraction inhibition model using a virtual pharmacokinetic (PK) compartment combined with an indirect response model and performed model diagnostics using goodness-of-fit analysis, visual predictive checks (VPC), and bootstrap analysis. The CMAP and DAS profiles were dose-dependent, with recovery times varying depending on the administered dose. The final K-PD model effectively characterized the data and provided insights into species-specific differences in the PK and PD parameters. Overall, this study demonstrated the utility of PK-PD modeling in understanding the effects of BoNT/A and provides a foundation for future research on other BoNT/A products.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"45 4-6","pages":"190-200"},"PeriodicalIF":1.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730962","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}
Yi Rong, Nanxi Li, Xuan Qiao, Lei Yang, Peng Han, Zhiyun Meng, Hui Gan, Zhuona Wu, Xiaoxia Zhu, Yunbo Sun, Shuchen Liu, Guifang Dou, Ruolan Gu
{"title":"Icaritin exhibits potential drug–drug interactions through the inhibition of human UDP-glucuronosyltransferase in vitro","authors":"Yi Rong, Nanxi Li, Xuan Qiao, Lei Yang, Peng Han, Zhiyun Meng, Hui Gan, Zhuona Wu, Xiaoxia Zhu, Yunbo Sun, Shuchen Liu, Guifang Dou, Ruolan Gu","doi":"10.1002/bdd.2397","DOIUrl":"10.1002/bdd.2397","url":null,"abstract":"<p>Icaritin is a prenylflavonoid derivative of the genus Epimedium (Berberidaceae) and has a variety of pharmacological actions. Icaritin is approved by the National Medical Products Administration as an anticancer drug that exhibits efficacy and safety advantages in patients with hepatocellular carcinoma cells. This study aimed to evaluate the inhibitory effects of icaritin on UDP-glucuronosyltransferase (UGT) isoforms. 4-Methylumbelliferone (4-MU) was employed as a probe drug for all the tested UGT isoforms using in vitro human liver microsomes (HLM). The inhibition potentials of UGT1A1 and 1A9 in HLM were further tested by employing 17β-estradiol (E2) and propofol (PRO) as probe substrates, respectively. The results showed that icaritin inhibits UGT1A1, 1A3, 1A4, 1A7, 1A8, 1A10, 2B7, and 2B15. Furthermore, icaritin exhibited a mixed inhibition of UGT1A1, 1A3, and 1A9, and the inhibition kinetic parameters (K<sub>i</sub>) were calculated to be 3.538, 2.117, and 0.306 (μM), respectively. The inhibition of human liver microsomal UGT1A1 and 1A9 both followed mixed mechanism, with K<sub>i</sub> values of 2.694 and 1.431 (μM). This study provides supporting information for understanding the drug–drug interaction (DDI) potential of the flavonoid icaritin and other UGT-metabolized drugs in clinical settings. In addition, the findings provide safety evidence for DDI when liver cancer patients receive a combination therapy including icaritin.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"45 3","pages":"149-158"},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417543","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}