Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m

Abstract

Background: This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m.

Methods and results: The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K_a and C_max of norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t_1/2 and Vd were significantly increased (p<0.05).

Conclusions: These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.

Keywords: High altitude; MRP2 expression changes; Norfloxacin; Pharmacokinetics; Physiological changes.