Changes in pharmacokinetics of single dose of fentanyl in simulated high altitude in rats
10.16016/j.2097-0927.202310018
- VernacularTitle:大鼠芬太尼单次给药在模拟高原环境中的药代动力学改变
- Author:
Yukun REN
1
,
2
;
Zhuo WANG
;
Xudong XIAO
;
Zonghong LONG
;
Yu LI
;
Qiuyue WANG
;
Hong LI
;
Jiaxing LIAO
;
Rong ZHANG
Author Information
1. 400037 重庆,陆军军医大学(第三军医大学)第二附属医院药剂科
2. 250031 济南,联勤保障部队第九六○医院麻醉科
- Keywords:
fentanyl;
high altitude;
pharmacokinetics;
hepatic blood flow;
CYP3A1
- From:
Journal of Army Medical University
2024;46(7):732-737
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.
