Comparisons of pharmacokinetics and NO-releasing of nitrofibriate and fenofibrate after oral administration in rats.
Nitrofibriate, a new compound of hypolipidemic, is modified based on fenofibrate. Both of them are used for prevention and treatment of cardiovascular diseases. In this study, an accurate and sensitive analytical method of reversed-phase high-performance liquid chromatography was developed to determine fenofibric acid, which is an active metabolite of both nitrofibriate and fenofibrate in rat plasma. This method was validated and successfully applied to pharmacokinetic study of nitrofibriate and fenofibrate after oral administration. The results suggested that the pharmacokinetic behavior of nitrofibriate followed a nonlinear process, while fenofibrate was linear, demonstrating that the two drugs were different in pharmacokinetic behaviors. Moreover, the effect of fenofibrate and nitrofibriate on releasing NO in rat serum was explored. This study showed that nitrofibriate, as a nitric oxide donor, could slowly release nitric oxide in vivo. This study provided a biopharmaceutical basis for further study of nitrofibriate.
Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China.
Yujie
Y
Yang
Sichuan Industrial Institute of Antibiotics, Chengdu, 610051, Sichuan, China.
Qiang
Q
Cheng
Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China.
Xiumei
X
Liu
Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China.
Zejuan
Z
Liu
Department of Pharmacy, People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, 666100, Yunnan, China.
Tingting
T
Li
Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China.
Xuehua
X
Jiang
Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, 610041, Sichuan, China.
Ling
L
Wang
D000284:Administration, Oral; D000818:Animals; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D009574:Nitro Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D009574:Nitro Compounds; C000614033:nitrofibriate; D009569:Nitric Oxide; D011345:Fenofibrate
RP-HPLC; nitrofibriate; no; pharmacokinetics