The impact of simulated tropical island environment on the pharmacokinetic characteristics and therapeutic effect of oral celecoxib in rat models of inflammatory pain
Objective:To investigate the effects of a simulated tropical island environment on the pharmacokinetics and efficacy of orally administered celecoxib (CXB) in inflammatory pain rats. Methods:Sixty-six male SD rats were randomly divided into a simulated tropical island environment group (STIE group) and a control group and were housed in their respective environment for three days. Serum drug concentrations were determined after oral administration of CXB in 36 rats,while 30 rats were used to establish an inflammatory pain model,and pain thresholds were measured. Results:The simulated island environment altered the pharmacokinetic characteristics of CXB,specifically,in the STIE group at medium to high doses,the terminal elimination half-life (t1/2) was reduced,and the area under the curve (AUC) values AUC (0-t) and AUC (0-∞) were significantly lower than those of the control group,while the clearance rate (CL) was significantly higher. Pain threshold assessments indicated that the pain thresholds of the inflammatory pain rats in the STIE group were significantly lower than those of the control group on days 3 to 5 post-CXB injection. Furthermore,the simulated island environment increased the expression of the key metabolic enzyme CYP2C9 in liver and led to elevated serum inflammatory factors. Conclusion:The simulated tropical island environment accelerated the metabolic rate of CXB and diminished its anti-inflammatory and analgesic effects.
tropical island environmenthigh temperature and high humiditycelecoxibpharmacokineticpain thresholdinflammatory factorrat
万方数据
维普
