Nonclinical Pharmacokinetics of OLX702A-075-16, N-Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA)
- 주제(키워드) Pharmaockinetics , siRNA
- 주제(DDC) 615.1
- 발행기관 아주대학교 일반대학원
- 지도교수 김소희
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 박사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034454
- 본문언어 한국어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
목차
I. Introduction 1
II. Materials and methods 5
A. Chemicals and Reagents 5
B. Preparation of GalNAc-asiRNA 5
C. Quantification of OLX702A-075-16 in Plasma, Urine and Tissue Samples 7
D. LC-HRMS based Metabolite Profiling of OLX702A-075-16 in Biological Matrices 9
E. In vitro Blood-to-Plasma Ratio 10
F. In vitro Plasma Protein Binding 11
G. Nonclinical In vivo Pharmacokinetic Studies 12
H. Model Regression 14
I. Pharmacokinetic Analysis 14
III. Results 16
A. Bioanalytical method qualification 16
B. In vitro assessment 28
C. Absorption and Distribution of OLX702A-075-16 in Mice 38
D. Absorption and Distribution of OLX702A-075-16 in Rats 41
E. OLX702A-075-16 Metabolism in Mice and Rats 48
F. Renal Excretion in Rats 59
G. Comparison of plasma pharmacokinetics of OLX702A-075-16 to other GalNAc-siRNAs 61
IV. Discussion 64
V. Conclusion 70
VI. Reference 71
