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Rat 동물모델에서 Tofacitinib의 용량의존적 Parmacokinetics
- Subtitle
- 낮은 생체 이용률에 간과 위장관 초회통과효과의 영향
- Alternative Title
- Dose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Gastrointestinal First-Pass Effect on Low Bioavailability
- Author(s)
- 이지상
- Alternative Author(s)
- Lee Ji Sang
- Advisor
- 김소희
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2018-02
- Language
- kor
- Alternative Abstract
- 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.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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