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Rat 동물모델에서 Tofacitinib의 용량의존적 Parmacokinetics
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 김소희 | - |
| dc.contributor.author | 이지상 | - |
| dc.date.accessioned | 2018-11-08T08:12:04Z | - |
| dc.date.available | 2018-11-08T08:12:04Z | - |
| dc.date.issued | 2018-02 | - |
| dc.identifier.other | 27538 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/11598 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학과,2018. 2 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 II. METHOD 3 A. Chemicals 3 B. Animals 3 C. Evaluate pharmacokinetics of tofacitinib after intravenous and oral administration in rat model 3 D. Measurement of tofacitinib concentration in rat tissues (organs) after intravenous administration 4 E. Evaluation of hepatic first-pass effect of tofacitinib 5 F. Evaluation of gastric and intestinal first-pass effect of tofacitinib 5 G. Biliary excretion of tofacitinib using rat model 6 H. HPLC analysis of tofacitinib 6 I. Pharmacokinetics analysis 7 J. Statistical analysis 7 III. RESULTS 9 A. Pharmacokinetics of tofacitinib after intravenous administration using rat model 9 B. Pharmacokinetics of tofacitinib after oral administration using rat model 13 C. Measurement of tofacitinib concentration in rat tissues (organs) after intravenous administration 16 D. Evaluation of hepatic first-pass effect of tofacitinib 18 E. Evaluation of gastric and intestinal first-pass effect of tofacitinib 21 F. Biliary excretion of tofacitinib using rat model 24 IV. DISCUSSION 25 V. CONCLUSION 27 REFERENCES 28 KOREAN ABSTRACT 30 | - |
| dc.language.iso | kor | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Rat 동물모델에서 Tofacitinib의 용량의존적 Parmacokinetics | - |
| dc.title.alternative | Dose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Gastrointestinal First-Pass Effect on Low Bioavailability | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Lee Ji Sang | - |
| dc.contributor.department | 일반대학원 약학과 | - |
| dc.date.awarded | 2018. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 800477 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027538 | - |
| dc.subject.keyword | Tofacitinib | - |
| dc.subject.keyword | Dose-dependent pharmacokinetics | - |
| dc.subject.keyword | First-pass effect | - |
| dc.subject.keyword | Low-bioavailability | - |
| dc.description.alternativeAbstract | Tofacitinib was indicated dependence on the dose increase in both cases of intravenous administration and oral administration. One of the dose-dependent pharmacokinetic parameter, the area under the plasma tofacitinib concentration-time curve from time zero to infinity (AUC0-∞), was meaningfully higher at 50 mg/kg dose of tofacitinib than at 5, 10 and 20 mg/kg (283, 342, 381 and 776 ug∙min/mL for 5, 10, 20 and 50 mg/kg, respectively, dose-normalized at 10 mg/kg) in intravenous administration study. In oral administration study, also the AUC0-∞ was meaningfully higher at 100 mg/kg dose of tofacitinib than at 10, 20 and 50 mg/kg (99.4, 151, 228 and 413 ug∙min/mL for 10, 20, 50 and 100 mg/kg, respectively, dose-normalized at 10 mg/kg). The absolute oral bioavailability (F) was about 29.1% at 10 mg/kg dose of todacitinib in rat. For first-pass effect study, the AUC0-∞ values were compared between these group which administered by intravenous, intraportal, intraportal, intraduodenal and intragastric route, respectively. The hepatic first-pass effect of tofacitinib was calculated about 41.9% and the intestinal first-pass effect of tofacitinib was calculated about 49.2% using rat model. The gastric first-pass effect was negligible. Consequently, the reasons of nonperfect F value were evaluated to be owing to the high hepatic and intestinal first-pass effect. | - |
| dc.title.subtitle | 낮은 생체 이용률에 간과 위장관 초회통과효과의 영향 | - |
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- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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