Rat 동물모델에서 Tofacitinib의 용량의존적 Parmacokinetics

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dc.contributor.advisor김소희-
dc.contributor.author이지상-
dc.date.accessioned2018-11-08T08:12:04Z-
dc.date.available2018-11-08T08:12:04Z-
dc.date.issued2018-02-
dc.identifier.other27538-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/11598-
dc.description학위논문(석사)--아주대학교 일반대학원 :약학과,2018. 2-
dc.description.tableofcontentsI. 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.isokor-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.titleRat 동물모델에서 Tofacitinib의 용량의존적 Parmacokinetics-
dc.title.alternativeDose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Gastrointestinal First-Pass Effect on Low Bioavailability-
dc.typeThesis-
dc.contributor.affiliation아주대학교 일반대학원-
dc.contributor.alternativeNameLee Ji Sang-
dc.contributor.department일반대학원 약학과-
dc.date.awarded2018. 2-
dc.description.degreeMaster-
dc.identifier.localId800477-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027538-
dc.subject.keywordTofacitinib-
dc.subject.keywordDose-dependent pharmacokinetics-
dc.subject.keywordFirst-pass effect-
dc.subject.keywordLow-bioavailability-
dc.description.alternativeAbstractTofacitinib 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.subtitle낮은 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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