Effects of vitexicarpin on the pharmacokinetics of sitagliptin in acute renal failure rats
- 주제(키워드) sitagliptin , vitexicarpin , pharmacokinetics , acute renal failure , renal protective effect
- 주제(DDC) 651.1
- 발행기관 아주대학교 일반대학원
- 지도교수 김소희
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 석사
- 학과 및 전공 일반대학원 바이오헬스규제과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034516
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Sitagliptin is a DPP-4 inhibitor used to improve glycemic control in patients with type 2 diabetes, predominantly eliminated through renal excretion. When renal complications arise in diabetic patients leading to renal failure, the pharmacokinetics of sitagliptin can be altered, thereby increasing the risk of toxicity. Vitexicarpin (VTX), a naturally occurring flavonoid, is recognized for its anti- inflammatory and antioxidant properties that support renal recovery. This study investigates the pharmacokinetic alterations of sitagliptin administered in conjunction with vitexicarpin in a cisplatin-induced acute renal failure (ARF) model. Preliminary experimental findings suggest that the ARF group showed a decrease in creatinine clearance (CLCR), elevated blood urea nitrogen (BUN) and serum creatinine (SCR) levels in comparison to the control group (CON). In contrast, the ARF-VTX group demonstrated renal function recovery, evidenced by reduced SCR and BUN levels alongside a rise in CLCR. In pharmacokinetic studies, the ARF group showed lower clearance rates (CL), renal clearance rates (CLR), non-renal clearance rates (CLNR), and 24-hour excretion amounts (Ae0-24h) in both intravenous and oral administrations relative to the control group. As a consequence, there was a rise in terminal half-life (T1/2) and area under the curve (AUC). Conversely, the ARF-VTX group exhibited a recovery in CL, CLR, CLNR, and Ae0-24h due to the nephroprotective effects of vitexicarpin, leading to a decrease in both T1/2 and AUC. Furthermore, in vitro studies revealed that the levels of CYP3A1/2 and CYP2C11 expression, as well as hepatic enzyme activity, were reduced in the microsomes of the ARF group, whereas these factors were elevated in the ARF-VTX group. Key words: sitagliptin, vitexicarpin, pharmacokinetics, acute renal failure, renal protective effect.
more목차
I. INTRODUCTION 1
II. METHOD 4
A. Chemicals 4
B. Animals 4
C. Induction of acute renal failure 5
D. Preliminary study 5
E. Intravenous and oral of sitagliptin 6
F. HPLC analysis of sitagliptin 7
G. Pharmacokinetics analysis 8
H. Measurement of Vmax, Km and CLint in hepatic and intestinal microsomes 8
I. Immunoblot analysis 9
J. Statistical analysis 10
III. RESULT 11
A. Preliminary study 11
B. Pharmacokinetics of sitagliptin after intravenous administration 14
C. Pharmacokinetics of sitagliptin after oral administration 18
D. Measurement of Vmax, Km and CLint in hepatic and intestinal microsomes 21
E. Protein production of CYP isozymes 23
IV. DISCUSSION 25
V. CONCLUSION 29
REFERENCES 30
KOREAN ABSTRACT 36
