Hongxia Jia, Axel Facius, Rachel Jennings, Yaming Hang, Jaya Padmanabhan, Niraj M Shanbhag, Brian T Harel, Arthur Simen, Wei Yin
{"title":"Population Pharmacokinetic and Exposure-Response Analysis of the Cognitive Effects of TAK-071 in Participants With Parkinson Disease and Cognitive Impairment.","authors":"Hongxia Jia, Axel Facius, Rachel Jennings, Yaming Hang, Jaya Padmanabhan, Niraj M Shanbhag, Brian T Harel, Arthur Simen, Wei Yin","doi":"10.1002/cpdd.1579","DOIUrl":"https://doi.org/10.1002/cpdd.1579","url":null,"abstract":"<p><p>TAK-071 is a novel muscarinic M<sub>1</sub> positive allosteric modulator under investigation for the treatment of cognitive impairment and falls associated with Parkinson disease (PD). This study evaluated population pharmacokinetics of TAK-071 following single (1-160 mg) and multiple (3-15 mg once daily) oral-dose TAK-071 in 112 healthy participants and 53 participants with PD from Phase 1 and Phase 2 studies. A 1-compartment model with a delayed absorption phase adequately described TAK-071 pharmacokinetics. Age, body weight, dose, and formulation were significant covariates. Model simulations indicated that age-adjusted dosing is unnecessary. An exposure-response relationship on cognitive function (attention, executive function, memory, global) was evaluated. Benefits were observed on attention, executive function, and global cognition, and these plateaued between 5 and 7.5 mg once daily, supporting a dose of 7.5 mg for future clinical studies, as 7.5 mg was well tolerated. As patients with PD can have an increased risk of falls, the relationship between cognitive function and risk of falls, as assessed by stride time variability, was explored. Cognition response for the attention domain score showed consistent and sustained improvement in stride time variability compared with when no response was observed, supporting further investigation of TAK-071 in PD for the risk of falls.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706595","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":"Comparative Pharmacodynamic Bioequivalence Study of Enoxaparin Sodium 100 mg/1 mL Solution for Injection in Prefilled Syringe in Healthy Volunteers Under Fasting Conditions.","authors":"Naba Kumar Talukdar, Shailesh Sonar, Nisha Pal, Uilberson Silva","doi":"10.1002/cpdd.1565","DOIUrl":"https://doi.org/10.1002/cpdd.1565","url":null,"abstract":"<p><p>This study evaluated the bioequivalence of enoxaparin sodium 100 mg/1 mL solution for injection in a prefilled syringe manufactured by a generic company was compared with the reference product of the same dosage form, in healthy adult volunteers under fasting conditions. The comparison focused on pharmacodynamic (PD) parameters. This open-label, randomized, balanced, 2-treatment, 2-period, single-dose, crossover study involved 60 healthy volunteers. No serious adverse events were reported. Chromogenic assay techniques were used for sample analysis. The linearity range for PD parameters was from 0.100 to 0.800 IU/mL for anti-factor IIa activity, from 0.100 to 0.800 IU/mL for anti-factor Xa activity, and from 750.000 to 10,000.000 pg/mL for tissue factor pathway inhibitor quantification. Statistical analysis was conducted using SAS software Version 9.4. The PD parameters evaluated included maximum observed activity concentration, area under the effect curve from time 0 to time t, median time to maximum concentration, and terminal elimination half-life for anti-factor Xa and anti-factor IIa activity. The 95% confidence intervals for the geometric mean ratio of log-transformed PD parameters between the test and reference products for anti-factor Xa and anti-factor IIa activities were within the range of 80%-125%. It was concluded that the test formulation is bioequivalent to the reference formulation of 100 mg/1 mL solution for injection in a prefilled syringe, under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689107","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}
Thomas N Kakuda, Nicole Harasym, Annemie Buelens, Ariane Kahnt, Caroline Feys, Ami Nilsson, Nele Goeyvaerts, Tristan Baguet, Tine De Marez, Guillermo Herrera-Taracena, Freya Rasschaert
{"title":"Pharmacokinetics, Safety, and Tolerability of Different Maintenance Dose Regimens of Mosnodenvir (JNJ-1802) in Healthy Adult Participants.","authors":"Thomas N Kakuda, Nicole Harasym, Annemie Buelens, Ariane Kahnt, Caroline Feys, Ami Nilsson, Nele Goeyvaerts, Tristan Baguet, Tine De Marez, Guillermo Herrera-Taracena, Freya Rasschaert","doi":"10.1002/cpdd.1574","DOIUrl":"https://doi.org/10.1002/cpdd.1574","url":null,"abstract":"<p><p>Dengue virus infection has become a global health concern, and no dengue-specific treatment is available. Mosnodenvir is a pan-serotypic dengue antiviral in clinical development. In this Phase 1, open-label study (NCT05201937), high- and low-dose weekly, and twice weekly maintenance doses (MDs) of mosnodenvir were evaluated following a twice daily loading dose (LD) over 2 days. The utility of a convenient capillary blood sampling device (TASSO-M20) was also explored. Healthy adults were sequentially assigned to receive: 450 mg twice daily LD, 900 mg once weekly MD; 450 mg twice daily LD, 450 mg twice weekly MD; 150 mg twice daily LD, 300 mg once weekly MD; or 150 mg twice daily LD, 150 mg twice weekly MD. Mosnodenvir exposure rapidly increased with LD and was maintained during the MD phase. In general, mosnodenvir increased in a dose-proportional manner with similar areas under the concentration-time curve between once weekly and twice weekly MD. The mean terminal elimination half-life across treatments was 6.7-8.7 days, supporting less frequent dosing. Safety and tolerability were similar across all treatment regimens. TASSO-M20 was preferred over venipuncture by participants. In summary, mosnodenvir administered weekly or biweekly achieved pharmacokinetic exposures that were found to be safe and well tolerated.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636383","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}
Usok Hyun, Seongnam Chu, Sungyun Kim, Jung-Ki Hong, Taeyoung Kim, In-Soo Yoon, Jung-Jin Kim, Hyun-Jong Cho
{"title":"Pharmacokinetic and Bioequivalence Evaluation of Two Sitagliptin Tablets With Different Salts in Healthy Subjects.","authors":"Usok Hyun, Seongnam Chu, Sungyun Kim, Jung-Ki Hong, Taeyoung Kim, In-Soo Yoon, Jung-Jin Kim, Hyun-Jong Cho","doi":"10.1002/cpdd.1573","DOIUrl":"https://doi.org/10.1002/cpdd.1573","url":null,"abstract":"<p><p>The objective of the current study was to evaluate the rate and extent of absorption of a test formulation (sitagliptin hydrochloride) and a reference formulation (sitagliptin phosphate). An open-label, randomized, single-dose, single-center, 2-sequence, 2-period, and cross-over phase 1 study was implemented to assess the pharmacokinetic bioequivalence of the test and reference formulations containing a single dose of sitagliptin 100 mg in 32 healthy volunteers under fasting conditions. The differences between the test and reference formulations in terms of the area under the curve from dosing to the time of the last measured concentration (AUC<sub>last</sub>) and the maximum concentration (C<sub>max</sub>) were found to be not significant. The 90% confidence intervals of sitagliptin Ln-transformed AUC<sub>last</sub> and C<sub>max</sub> were within the pharmacokinetic bioequivalence acceptance range of 80%-125%. The test formulation with sitagliptin hydrochloride was bioequivalent to the reference formulation with sitagliptin phosphate in healthy male volunteers under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607669","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}
Yanjun Jiang, Lu Wang, Jia Liu, Lizhen Jiang, Kang Li, Zhanhui Lv, Sufeng Zhou, Feng Shao
{"title":"Physiologically Based Pharmacokinetic Modeling to Evaluate Drug-Drug Interactions of Tacrolimus With Ritonavir, a CYP3A Irreversible Inhibitor: Applications for Dosing Optimization in Transplant Patients.","authors":"Yanjun Jiang, Lu Wang, Jia Liu, Lizhen Jiang, Kang Li, Zhanhui Lv, Sufeng Zhou, Feng Shao","doi":"10.1002/cpdd.1572","DOIUrl":"https://doi.org/10.1002/cpdd.1572","url":null,"abstract":"<p><p>Immunosuppressant tacrolimus is frequently coadministered with other drugs in clinical practice. Ritonavir is a CYP3A irreversible inhibitor that is used in combination with nirmatrelvir for the treatment of COVID-19 in nirmatrelvir/ritonavir. We aimed to apply physiologically based pharmacokinetic (PBPK) modeling to investigate the dose adjustment strategy for tacrolimus during short-term coadministration with ritonavir. PBPK models for tacrolimus and ritonavir were successfully developed based on in vitro and clinical data, and were used to predict drug-drug interaction levels via metabolic enzyme inhibition mechanisms. The recommended dose strategy based on our model simulation is to hold tacrolimus during nirmatrelvir/ritonavir treatment and restart half of the initial dose on day 3 after the 5-day ritonavir course, followed by resuming the full dose on day 5. This administration strategy can maintain trough concentrations of tacrolimus within the therapeutic window during and after ritonavir treatment.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607670","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}
Kelong Han, Ronald D D'Amico, William R Spreen, Susan L Ford
{"title":"Strategies to Manage Dosing Deviations and Interruptions of Cabotegravir Long-Acting Intramuscular Injections.","authors":"Kelong Han, Ronald D D'Amico, William R Spreen, Susan L Ford","doi":"10.1002/cpdd.1568","DOIUrl":"https://doi.org/10.1002/cpdd.1568","url":null,"abstract":"<p><p>Long-acting cabotegravir is approved for HIV treatment and prevention. To guide management of dosing deviations and interruptions, concentration-time profiles for monthly and every 2 months regimens were simulated using a population pharmacokinetic (PPK) model. Adequate exposure was defined as trough concentration (C<sub>tau</sub>) >0.45 µg/mL (observed 5th percentile of first C<sub>tau</sub> in pivotal studies) in >95% of subjects and maximum concentration (C<sub>max</sub>) <13.1 µg/mL (highest observed median steady-state C<sub>max</sub> in previous studies) in >50% of subjects. Simulations showed: (1) median C<sub>max</sub> remained ≤6.35 µg/mL after doubled doses; (2) C<sub>tau</sub> was suboptimal after half dose at first injection but recovered with a corrective dose; (3) injection delays ≤7 days maintained adequate C<sub>tau</sub>, while longer delays caused extended low-exposure periods (≤23 days for 1-month delay, ≤83 days for 3-month delay); (4) reinitiating loading dose after delays >1 month led to higher exposure than continuing injections and may mitigate efficacy loss and resistance risks; and (5) oral bridging (30 mg daily) maintained adequate exposure during delays. Recommended strategies include no action for higher-than-planned doses, corrective dosing for lower-than-planned doses, strict adherence to schedule, reinitiating the loading dose after delays >1 month, and oral bridging. These findings were incorporated into product labeling and can inform next-generation cabotegravir and other long-acting agent development.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607671","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":"Pharmacokinetics and Safety of Armodafinil in Chinese Healthy Humans After Multiple-Dose Oral Administration.","authors":"Liwei Lang, Yuan Dong, Zhenzhen Zhu, Shanwei Zhu, Hongyan Wang, Jingfeng Bi, Fang Wang","doi":"10.1002/cpdd.1527","DOIUrl":"https://doi.org/10.1002/cpdd.1527","url":null,"abstract":"<p><p>Armodafinil, the R-enantiomer of modafinil that promotes wakefulness, was studied regarding its pharmacokinetics and safety in healthy Chinese subjects after multiple-dose oral administration (200 mg daily for 7 days). Twelve subjects participated in this single-center, self-contrast study. The plasma concentrations of armodafinil and its metabolites (R-modafinil acid and modafinil sulfone) were measured by ultra-performance liquid chromatography-tandem mass spectrometry, and drug safety was evaluated during the study. The steady-state accumulation ratio of armodafinil was 1.5, and its metabolites also accumulated with ratios of 1.3 and 7.8, respectively. Although the mean steady-state half-life was similar to that after a single dose, the area under the concentration-time curve, maximum plasma concentration, and clearance of armodafinil changed significantly after multiple dosing. The drug was safe with no serious adverse events, yet fever occurred in 6 subjects, which was not reported before. Modafinil sulfone had significant accumulation, implying the need for further study on its central nervous system-activating properties in Chinese patients.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559432","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 Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-101, an RNAi Therapeutic Targeting HBV Infection.","authors":"Jianxiong Zhang, Jiangshuo Li, Le Wu, Yuqin Song, Xiao Li, Qiannan Gao, Jingxuan Wu, Dong Wang, Zhipeng Zhang, Shanzhong Zhang, Lijuan Ding, Yanqin Ma, Hong Ma, Jidong Jia, Ruihua Dong","doi":"10.1002/cpdd.1569","DOIUrl":"https://doi.org/10.1002/cpdd.1569","url":null,"abstract":"<p><p>HT-101, a liver-targeted N-acetylgalactosamine-conjugated ribonucleic acid interference therapeutic, exhibits promising potential for the treatment of chronic hepatitis B virus infection. This randomized, double-blind, placebo-controlled, and single-ascending-dose Phase Ia study included 50 healthy volunteers. Regarding methods, 2 subjects received a single subcutaneous dose of HT-101 at 25 mg, while 48 volunteers were randomized (6:2 active:placebo) in the remaining 6 cohorts to receive a single subcutaneous dose of HT-101 (50-800 mg) or placebo. Afterward, serial blood samples were obtained for pharmacokinetic determination across a 48-hour postdose period. Safety assessments included clinical laboratory measures, vital signs, and 12-lead electrocardiogram before and after dosing. As a result, plasma pharmacokinetics characterized by functional antisense strand revealed a median time to peak plasma concentration of 2.5-6.0 hours, and a short median plasma half-life of 2.50-6.14 hours. It is underlined that peak and total plasma exposure to HT-101 increased in a slightly greater-than-dose-proportional manner following 25-800 mg administered subcutaneously. Moreover, a single dose of HT-101 at 25-800 mg was safe and well tolerated in healthy Chinese volunteers. These data can support further clinical development of HT-101 for hepatitis B virus infection treatment.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552459","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}
Hegui Yan, Yu Peng, Zhixiang Pan, Yiyi Wang, Quan Li, Guan Liu
{"title":"Pharmacokinetics and Bioequivalence Evaluation of Two Different Aildenafil Citrate Tablet Formulations in Healthy Chinese Male Subjects Under Fasting and Fed Conditions.","authors":"Hegui Yan, Yu Peng, Zhixiang Pan, Yiyi Wang, Quan Li, Guan Liu","doi":"10.1002/cpdd.1571","DOIUrl":"https://doi.org/10.1002/cpdd.1571","url":null,"abstract":"<p><p>Aildenafil citrate is a novel and potent phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction (ED). This study evaluates the pharmacokinetics and bioequivalence of 2 formulations of aildenafil citrate tablets (30 and 60 mg) in healthy Chinese male subjects under both fasting and fed conditions. A single-center, randomized, open-label, 2-period crossover design was employed, with 78 participants enrolled, including 30 in the fasting condition and 48 in the fed condition. Blood samples were collected at multiple time points for pharmacokinetic analysis, which included C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> as the primary parameters. The results demonstrated that the pharmacokinetic profiles of the test and reference formulations were comparable in both the fasting and fed states, with 90% confidence intervals for the geometric mean ratios of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> falling within the 80%-125% range, confirming bioequivalence. Although food intake slightly delayed the time to peak concentration and reduced the absorption rate, it did not significantly affect the overall bioavailability. Both formulations were well tolerated, with adverse events being mild and resolving spontaneously. This study provides evidence supporting the bioequivalence of the 2 aildenafil citrate formulations and their interchangeability for clinical use in treating ED.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552508","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}
Mingqi Chen, Weixiong Liu, Yiyun Wang, Jianyan Guo, Yuling Luo, Jianfen Su, Yanping Mu
{"title":"Bioequivalence and Pharmacokinetics of Ibuprofen Extended-Release Capsules in Healthy Chinese Volunteers Under Fasting and Postprandial Conditions.","authors":"Mingqi Chen, Weixiong Liu, Yiyun Wang, Jianyan Guo, Yuling Luo, Jianfen Su, Yanping Mu","doi":"10.1002/cpdd.1570","DOIUrl":"https://doi.org/10.1002/cpdd.1570","url":null,"abstract":"<p><p>The objective of this study was to evaluate the pharmacokinetics and safety of a generic and a branded reference formulation of ibuprofen extended-release capsules. Bioequivalence between the 2 products was assessed through a clinical trial conducted in healthy Chinese volunteers. The study was divided into 2 groups: fasting and postprandial. Thirty-two volunteers were enrolled in the fasting group and 24 in the postprandial group. Participants in each group were randomly assigned to receive either the generic (test) or branded (reference) product. Following the first dosing cycle, a 7-day washout period was observed. Afterward, subjects crossed over to the alternate treatment and completed a second cycle. Pharmacokinetic parameters were determined using plasma concentration-time profiles. These included the area under the plasma concentration-time curve during the dosing interval (AUC<sub>0-t</sub>), the AUC extrapolated to infinity (AUC<sub>0-∞</sub>), the maximum observed plasma concentration (C<sub>max</sub>), the time to reach C<sub>max</sub> (t<sub>max</sub>), and the elimination half-life (t₁/₂). The results demonstrated that the generic and reference ibuprofen extended-release capsules were bioequivalent in healthy Chinese volunteers under both fasting and postprandial conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539295","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}