Effect of amoxicillin on the expression of PEPT1 and pharmacokinetics upon acute hypoxia at high altitude in rat
10.16438/j.0513-4870.2017-0562
- VernacularTitle:高原急性缺氧对大鼠药物转运体PEPT1及阿莫西林药代动力学的影响
- Author:
Bing-feng LUO
1
;
Jun ZHANG
1
;
Tao YANG
2
;
Juan-hong ZHANG
1
;
Wen-bin LI
1
;
Chang WANG
1
;
Ming-xia ZHANG
1
;
Rong WANG
1
Author Information
1. PLA Key Laboratory of the Plateau of the Environmental Damage Control, Lanzhou General Hospital, Lanzhou Command, Lanzhou 730050, China
2. Department of Pharmacy, Gansu Provincial Maternity and Child Care Hospital, Lanzhou 730050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
acute hypoxia at high altitude;
peptide transporter;
expression change;
amoxicillin;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2017;52(11):1715-1721
- CountryChina
- Language:Chinese
-
Abstract:
The relationship between PEPT1 (peptide transporter) and drug efficacy has drawn more and more attention in the treatment of disease. PEPT1 represents a promising strategy for improvement of drug bioavailability and an important starting point for clinical rationalization of drug selection. The effect of PEPT1 on transport and pharmacokinetics of amoxicillin was investigated under hypoxia condition at high altitude in rat. The mRNA and protein expressions of PEPT1 were increased by 36.87%, 216.21%, 577.8% and 535.9% respectively in the hypoxia group in the small intestine and kidney of rats. However, the mRNA and protein expressions of PEPT1 were reduced by 43.90% and 84.7% in the liver. Compared with the control group, the AUC, tmax, Cmax, MRT and t1/2 of amoxicillin were significantly enhanced by 312.17%, 63.04%, 110.93%, 67.11% and 16.96% respectively in the hypoxia group, while the CL was significantly decreased by 74.51%. After acute exposure to high altitude, the expressions of drug transporter PEPT1 were distinctly changed in rat tissues, which can affect the pharmacokinetics of amoxicillin.
