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새로운 CCR-2 길항제, YJC-10592의 약물동력학 연구
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 김소희 | - |
| dc.contributor.author | 두은신 | - |
| dc.date.accessioned | 2018-11-08T08:18:31Z | - |
| dc.date.available | 2018-11-08T08:18:31Z | - |
| dc.date.issued | 2015-02 | - |
| dc.identifier.other | 19322 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/12684 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학,2015. 2 | - |
| dc.description.tableofcontents | ABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ LIST OF TABLES ⅶ ABBREVIATIONS ⅷ Ⅰ. INTRODUCTION 1 Ⅱ. MATERIALS AND METHODS 3 A. Chemicals 3 B. Animal 3 C. Preparation of standard solutions 3 D. Sample preparations 4 E. HPLC apparatus 4 F. Intravenous study 5 G. Oral study 6 H. Tissue distribution study 6 I. Pharmacokinetic analysis 7 J. Statistical analysis 8 Ⅲ. RESULTS 9 A. Validation of HPLC method 9 B. Intravenous study 18 C. Oral study 21 D. Tissues distribution study 24 Ⅳ. DISCUSSION 26 Ⅴ. CONCLUSION 28 REFERENCES 29 KOREAN ABSTRACT 32 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 새로운 CCR-2 길항제, YJC-10592의 약물동력학 연구 | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 약학 | - |
| dc.date.awarded | 2015. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 695567 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000019322 | - |
| dc.subject.keyword | YJC-10592 | - |
| dc.subject.keyword | CCR-2 antagonist | - |
| dc.subject.keyword | HPLC | - |
| dc.subject.keyword | pharmacokinetics | - |
| dc.subject.keyword | dose-dependent | - |
| dc.description.alternativeAbstract | YJC-10592, a novel chemokine receptor 2 (CCR-2) antagonist, was synthesized for the therapy of atopic dermatitis and asthma. To evaluate the pharmacokinetic characteristics of YJC-10592, a high-performance liquid chromatographic (HPLC) method was developed for the determination of YJC-10592 in rat plasma, urine and tissue homogenates using YJC-10450 as an internal standard. The mobile phase was gradient of 50 mM acetate buffer (pH 3.0) in acetonitrile at a flow rate of 1.0 ml/min. Chromatograms were monitored at 230 nm ultraviolet (UV) detector. The retention times were 8.0 in YJC-10592 and 6.3 min in the internal standard, respectively. And the detection limits of YJC-10592 were 0.05 g/ml in rat plasma and 0.2 g/ml in urine, respectively. The within- and between-day coefficients of variation (CV) of the analysis were commonly low (less than 13.6 %) for rat plasma and urine samples. After intravenous administration of YJC-10592, 5, 10 and 20 mg/kg, to rats, the pharmacokinetics of YJC-10592 was dose-dependent from 20 mg/kg dose. The values of the area under the plasma concentration-time curve from the time zero to the time infinite (AUC), the time-averaged total body (CL) and nonrenal (CLNR) clearance of YJC-10592 were dose-dependent from 20 mg/kg. CL and CLNR of YJC-10592 were significantly low at dose of 20 mg/kg compared to those at 5 and 10 mg/kg, suggesting that saturable metabolism might be involved. After YJC-10592 was orally administration at doses of 100 and 200 mg/kg, to rats, the absolute bioavailability (F) values (4.01 and 1.89% for 100 and 200 mg/kg, respectively) was low, taking into absorption of the drug from rat gastrointestinal tract (90.2 and 88.4% absorbed for 100 and 200 mg/kg, respectively) and first-pass metabolism in the liver, stomach and/or metabolism might be one reason for this result. YJC-10592 had a good affinity to almost all rat tissues studied except brain and this was supported by a relatively high value of the apparent volume of distribution at steady state (Vss) (890-1385 ml/kg) after intravenous administration of YJC-10592 to rats. | - |
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- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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