伊曲康唑对双氯芬酸在比格犬体内药动学的影响

Influence of Itraconazole on the Pharmacokinetics of Diclofenac in Beagle Dogs

目的:研究伊曲康唑对双氯芬酸钠在比格犬体内药动学参数的影响。方法:采用随机交叉试验方法,一组口服双氯芬酸钠,另一组同时口服双氯芬酸钠和伊曲康唑,清洗期1周后,两组交叉服用药物。用HPLC法测定比格犬合用伊曲康唑前后双氯芬酸的血药浓度,并对其药动学参数进行分析。结果:较单独给予双氯芬酸钠,合用伊曲康唑使双氯芬酸钠血药浓度曲线下面积(AUC_(0–∞))与最大血药浓度C_(max)分别降低31%和42%。而达峰时间和半衰期并无显著差异(P>0.05)。结论:伊曲康唑可能通过影响双氯芬酸的胃肠道吸收过程,来影响AUC_(0–∞)和C_(max)。

Objective： To investigate the potential effect of itraconazole on the pharmacokinetics of diclofenac sodium in Beagle dogs after oral co-administration. Methods： A randomized and crossover study was performed in Beagle dogs. One group was with oral administration of diclofenac sodium,and the other was with oral co-administration of diclofenac sodium and itraconazole. After 1-week wash-out,the two groups were cross taken the drugs. The blood concentration of diclofenac in Beagle dogs before and after the combination with itraconazole was determined by HPLC,and the pharmacokinetic parameters were analyzed. Results： When compared with that of diclofenac sodium alone,the AUC_（0–∞）and C_（max）of diclofenac in the combination was decreased by 31% and 42%,respectively,while no statistically significant differences were observed in Tmaxand t1 /2of diclofenac between the treatment regimens. Conclusion：Itraconazole can reduce the AUC_（0–∞）and C_（max）of diclofenac through the influence on GIT absorption of diclofenac.