Clinical Research and Regulatory Affairs最新文献_第10页

Dissolution of poorly water-soluble drugs in biphasic media using USP 4 and fiber optic system 使用usp4和光纤系统在双相介质中溶解水溶性差的药物

Clinical Research and Regulatory Affairs Pub Date : 2009-06-01 DOI: 10.1080/10601330902905887

S. Vangani, Xiaoling Li, Peter Zhou, M. Del-Barrio, R. Chiu, Nina S. Cauchon, P. Gao, Cesar Medina, B. Jasti

{"title":"Dissolution of poorly water-soluble drugs in biphasic media using USP 4 and fiber optic system","authors":"S. Vangani, Xiaoling Li, Peter Zhou, M. Del-Barrio, R. Chiu, Nina S. Cauchon, P. Gao, Cesar Medina, B. Jasti","doi":"10.1080/10601330902905887","DOIUrl":"https://doi.org/10.1080/10601330902905887","url":null,"abstract":"A novel in-vitro dissolution system based on the principle of flow-through technique has been designed to evaluate the in-vitro release rate of poorly water-soluble compounds. The flow through apparatus (USP 4) has been coupled with the compendial dissolution apparatus (USP apparatus 2). A bi-phasic dissolution medium is used to achieve sink conditions. The dissolved drug is continuously removed from the aqueous phase into the organic phase of the dissolution medium, mimicking the process of absorption in the systemic circulation. The in vitro release profiles obtained from this dissolution model was able to distinguish the formulation changes of several poorly water-soluble drugs from their dosage forms. For AMG 517, the model drug, excellent rank order correlation has been obtained between the in-vitro release and the in-vivo absorption of the drug from several different dosage forms and their formulations. In addition, for several commercial formulations, the model successfully discriminated between the bioequivalent and non-bioequivalent formulations.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"22 1","pages":"19 - 8"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83556508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

Certification in good clinical practice and clinical trial quality: A retrospective analysis of protocol adherence in four multicenter trials in the USA 良好临床实践和临床试验质量认证:美国四个多中心试验方案依从性的回顾性分析

Clinical Research and Regulatory Affairs Pub Date : 2009-06-01 DOI: 10.1080/10601330902911893

Jean-Marc C. Haeusler

{"title":"Certification in good clinical practice and clinical trial quality: A retrospective analysis of protocol adherence in four multicenter trials in the USA","authors":"Jean-Marc C. Haeusler","doi":"10.1080/10601330902911893","DOIUrl":"https://doi.org/10.1080/10601330902911893","url":null,"abstract":"Background: The value of training in Good Clinical Practice (GCP) for clinical research professionals is unknown. The objective of this study was to assess the impact of formal training in GCP on the quality of clinical trials. Methods: Retrospective analysis of data collected from four multicenter trials conducted in the US in 2008. Certification as Physician Investigator (CPI) or Clinical Research Coordinator (CCRC) was used as proof of formal training in GCP. Protocol adherence was used as a proxy for the quality of clinical trials and quantified by the number of protocol deviations. The primary variable for analysis was the number of protocol deviations per randomized subject and site. Results: A total of 1,418 subjects were randomized by 101 investigators (29% CPI) and 109 clinical research coordinators (29% CCRC), with 520 protocol deviations. Compared to “no certification”, the Odds Ratios (OR) for the incidence of protocol deviations were OR = 1.20 (95% Confidence Interval [0.852–1.688]; p NS) for “CCRC-only”, OR = 0.70 ([0.513–0.953]; p = 0.0256) for “CPI-only”, and OR = 0.37 ([0.273–0.507]; p < 0.0001) for “CCRC + CPI”. Conclusions: This pilot study showed that formal training in GCP has the potential to improve protocol adherence and clinical trial quality.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"20 1","pages":"20 - 23"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86811145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Physicians’ knowledge and attitudes toward scheduling 医生对日程安排的知识和态度

Clinical Research and Regulatory Affairs Pub Date : 2009-05-01 DOI: 10.1080/10601330902852725

Jonathon M Parker, E. Larrat

引用次数: 4

Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat. 大鼠静脉和口服给药后阿昔洛韦二肽酯前药及其代谢产物的处置动力学。

Clinical Research and Regulatory Affairs Pub Date : 2009-01-01 DOI: 10.1080/10601330903200684

Ravi S Talluri, Ripal Gaudana, Sudharshan Hariharan, Ritesh Jain, Ashim K Mitra

{"title":"Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat.","authors":"Ravi S Talluri, Ripal Gaudana, Sudharshan Hariharan, Ritesh Jain, Ashim K Mitra","doi":"10.1080/10601330903200684","DOIUrl":"https://doi.org/10.1080/10601330903200684","url":null,"abstract":"<p><p>The objective of this work was to study the disposition kinetics of valine-valine-acyclovir (VVACV), a dipeptide ester prodrug of acyclovir following intravenous and oral administrations in rat. A validated LC-MS/MS analytical method was developed for the analysis VVACV, Valine-Acyclovir (VACV), and Acyclovir (ACV) using a linear Ion Trap Quadrupole. ACV was administered orally for comparison purpose. In the VVACV group, both blood and urine samples and in the ACV group only blood samples were collected. All the samples were analyzed using LC-MS/MS. The LLOQ for ACV, VACV, and VVACV were 10, 10, and 50 ng/ml, respectively. Relevant pharmacokinetic parameters were obtained by non-compartmental analyses of data with WinNonlin. Following i.v. administration of VVACV, AUC(0-inf) (min*µM) values for VVACV, VACV, and ACV were 55.06, 106, and 466.96, respectively. The AUC obtained after oral administration of ACV was 178.8. However, following oral administration of VVACV, AUC(0-inf) values for VACV and ACV were 89.28 and 810.77, respectively. Thus the exposure of ACV obtained following oral administration of VVACV was almost 6-fold higher than ACV. This preclinical pharmacokinetic data revealed that VVACV has certainly improved the oral bioavailability of ACV and is an effective prodrug for oral delivery of ACV.</p>","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"26 3","pages":"65-72"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10601330903200684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29634920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Transdermal Delivery of Methotrexate Using Mixed Grades of Eudragit: Physico-Chemical, In-Vitro, and In-Vivo Evaluations 使用混合等级的乌龙茶经皮给药甲氨蝶呤:物理化学，体外和体内评价

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330801937544

Ashok R. Chandak, P. Verma

引用次数: 10

The Role of Inflammation in Tumor Progression: Targeting Tumor-Associated Macrophages 炎症在肿瘤进展中的作用:靶向肿瘤相关巨噬细胞

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330802208291

M. Varney, Rakesh K. Singh

引用次数: 2

Population Pharmacokinetics of Amikacin in Indian Pediatric Patients 阿米卡星在印度儿科患者中的人群药代动力学

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330802383441

Butchi Raju Akondi, R. Chodavarapu, K. Devarakonda

{"title":"Population Pharmacokinetics of Amikacin in Indian Pediatric Patients","authors":"Butchi Raju Akondi, R. Chodavarapu, K. Devarakonda","doi":"10.1080/10601330802383441","DOIUrl":"https://doi.org/10.1080/10601330802383441","url":null,"abstract":"The aim of this study was to describe population pharmacokinetics of amikacin in Indian pediatric population. Dosage adjustment based on individual pharmacokinetic parameters is of considerable importance for effective and safe use of drugs. Extensive work on amikacin and other aminoglycosides was carried out in different pediatric patient populations but no data are available in Indian pediatric patients. In the present study 74 steady state concentrations of amikacin were analyzed from 42 patients. Pharmacostatistical work was done by using NONMEM. The covariates evaluated in this study were age, body weight, height, and sex and creatinine clearance. The model found to best describe the data following FO method was: Clearance (CL) = θ1*(wt/14.2)*exp. (η1) and volume (V) = θ2*exp (η2) and following FOCE method was: Clearance (CL) = θ1*(age/5.38) + θ3*(wt/14.2)*exp.(η1) and volume(V) = θ2*exp(η2). The final model estimates of CL and V estimated by FO method were1.02 L/h and 4.55L respectively and by FOCE method were1.07L/hr and 4.91L respectively. These parameters are utilized for individualizing the loading and maintenance doses in pediatric patients.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"3 1","pages":"173 - 182"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90063149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Formulation and Clinical Evaluation Of Ultradeformable Liposomes in the Topical Treatment of Psoriasis 超成形脂质体局部治疗银屑病的配方及临床评价

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330701885116

K. Vanaja, R. H. Shobha Rani, S. Sacchidananda

{"title":"Formulation and Clinical Evaluation Of Ultradeformable Liposomes in the Topical Treatment of Psoriasis","authors":"K. Vanaja, R. H. Shobha Rani, S. Sacchidananda","doi":"10.1080/10601330701885116","DOIUrl":"https://doi.org/10.1080/10601330701885116","url":null,"abstract":"Ultradeformable liposomes of Methotrexate (MTX) were formulated to enhance its transdermal delivery in the treatment of psoriasis. Formulations were characterized for particle size, polydispersity index, morphology employing TEM and residual solvent analysis. The efficacy of topical liposomal MTX gel was compared with the commercially available plain MTX gel by clinically investigating the reduction in PASI score in psoriasis patients. Allergic contact sensitization potential of placebo ultradeformable liposomal gel was evaluated which showed that the placebo gel did not produce any reaction in the induction as well as challenge phase in 12 human volunteers. Open label, randomized parallel study was conducted in 25 patients. Baseline PASI score in the group receiving liposomal gel (0.25%) was 5.3 ± 1.027 and at the 10th week was reduced to 2.4 ± 0.625. In the case of the group applying plain MTX gel (1%), the baseline PASI score was 6.2 ± 0.17, reduced to 2.9 ± 0.79 at the 10th week. It was observed that liposomal MTX gel of 0.25% improved palmoplantar psoriasis in comparison with 1% plain MTX gel. Therefore, reducing the dose by entrapping MTX in liposomes improved the efficacy and patient compliance.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":"118 1","pages":"41 - 52"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85702265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Evaluation of Bioequivalence of Highly Variable Drugs 高度可变药物的生物等效性评价

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330802131451

L. Endrenyi, L. Tothfalusi

引用次数: 6

Comparison of Effect of Fasting and of Five Different Diets on the Bioavailability of Single Oral Dose of Amoxicillin 500 mg Capsule 空腹与5种不同膳食对阿莫西林500mg胶囊单次口服生物利用度影响的比较

Clinical Research and Regulatory Affairs Pub Date : 2008-01-01 DOI: 10.1080/10601330802064272

A. Khuroo, T. Monif, P. Verma, S. Gurule

引用次数: 2