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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국약제학회 Journal of Pharmaceutical Investigation Journal of Pharmaceutical Investigation 제50권 제6호
- 발행연도
- 2020.1
- 수록면
- 603 - 612 (10page)
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초록· 키워드
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Purpose Tofacitinib, a janus kinase (JAK) inhibitor, was developed for the treatment of rheumatoid arthritis. To evaluate its pharmacokinetic characteristics, a simple method of quantifying tofacitinib by high-performance liquid chromatography (HPLC) was developed to estimate its concentrations in rat plasma, urine and tissue homogenates. Methods Hydrocortisone was used as an internal standard. The mobile phase was an isocratic system of acetonitrile: 10 mM ammonium acetate, pH 5.0 (30.5:69.5, v/v), and the flow rate was 1.0 mL/min. Chromatograms were monitored by a UV detector at 287 nm. The retention times for tofacitinib and hydrocortisone were 7.21 and 11.3 min, respectively. Results The lower limits of quantification for tofacitinib in rat plasma and urine were 0.01 and 0.1 μg/mL, respectively. The intraday assay precisions (coefficients of variation) were generally low; 3.69?5.88% for rat plasma and 4.21?6.18% for rat urine. The corresponding values of interday assay precisions were 5.06% and 5.46%, respectively. Accuracies ranged from 92.9 to 107%, with no interference by endogenous substances. Tofacitinib has a short half-life (39.0 min) and was widely distributed in rat tissues. Conclusion This HPLC method is very simple and sensitive and can be applied to future preclinical and clinical investigations of tofacitinib.
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참고문헌 (21)
참고문헌 신청
Antonelli E / 2018 / Novel oral-targeted therapies for mucosal healing in ulcerative colitis / World J Gastroenterol 24:5322~5330
Boor PPC / 2017 / JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa / Transl Res 188:67~79
CDER / Guidance for industry: bioanalytical methods validation
Dowty ME / 2014 / Preclinical to clinical translation of tofacitinib, a janus kinase inhibitor, in rheumatoid arthritis / J Pharmacol Exp Ther 348:165~173
Dowty ME / 2014 / The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans / Drug Metab Dispos 42:759~773
Boor PPC / 2017 / JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa / Transl Res 188:67~79
CDER / Guidance for industry: bioanalytical methods validation
Dowty ME / 2014 / Preclinical to clinical translation of tofacitinib, a janus kinase inhibitor, in rheumatoid arthritis / J Pharmacol Exp Ther 348:165~173
Dowty ME / 2014 / The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans / Drug Metab Dispos 42:759~773
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