齐多夫定对大鼠内源性左卡尼汀水平及左卡尼汀药动学的影响

目的研究齐多夫定对大鼠内源性左卡尼汀水平及左卡尼汀药动学的影响。方法 Wistar大鼠18只,随机分为A、B、C 3组。A组为空白对照组,不给药;B组单独给予齐多夫定;C组联合给予齐多夫定和左卡尼汀。连续给药45 d,采用LC-MS/MS法测定和比较各组大鼠肌肉和心脏中内源性左卡尼汀水平。另取Wistar大鼠12只,随机分成2组,一组给予左卡尼汀,另一组联合给予左卡尼汀和齐多夫定,采用LC-MS/MS法分别测定2组大鼠给药后左卡尼汀血药质量浓度的经时变化,用DAS 2.1.1软件计算主要药动学参数,并进行统计分析和比较。结果大鼠长期给予齐多夫定后,肌肉中左卡尼汀水平较对照组显著降低,心脏中左卡尼汀水平无显著变化;联合给予齐多夫定和左卡尼汀后,大鼠肌肉中左卡尼汀水平与对照组比较差异无统计学意义,心脏中左卡尼汀水平显著升高。大鼠单独给予左卡尼汀和联合给予齐多夫定和左卡尼汀后的主要药动学参数差异无统计学意义。结论齐多夫定能抑制肌肉组织对左卡尼汀的摄取,接受齐多夫定治疗的同时补充左卡尼汀能减轻齐多夫定引起的不良反应,齐多夫定对大鼠体内左卡尼汀的药动学无显著影响。

Effects of zidovudine on the concentration of endogenous L-carnitine and pharmacokinetics of L-carnitine in rats

Objective To investigate the effects of zidovudine on the concentration of endogenous L-carnitine and pharmacokinetics of L-carnitine in rats. Methods Eighteen healthy male Wistar rats were randomly divided into 3 groups. Rats of group A were chosen as control group and administrated only by distilled water, rats of group B were administered zidovudine , and zidovudine and L-carnitine were administrated together to rats of group C. The administration process of the three groups lasted for 45 d, respectively. The concentrations of endogenous L-carnitine in muscle and heart were determined by LC-MS/MS and compared. Another twelve healthy male Wistar rats were randomly divided into 2 groups and received i.g. administration of L-carnitine alone or combination of L-carnitine with zidovudine, respectively. The concentrations of L-carnitine in rat plasma were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by DAS2.1.1 software. Results After long-term administration of zidovudine, the concentrations of L-carnitine in rat muscle were significantly decreased, while no change was observed in rat heart. After long-term administration of combination of L-carnitine with zidovudine, the concentrations of L-carnitine in muscle were no significant change, while a remarkable increase on L-carnitine concentrations was found in heart in comparison with control group. There was no significant difference between the pharmacokinetic parameters after oral administration of L-carnitine and the combination of L-carnitine with zidovudine. Conclusions Zidovudine can inhibit the uptake of L-carnitine in muscle. A moderate supplementation of L-carnitine may alleviate zidovudine-induced side effects in zidovudine-treated patients. There is no significant effect of zidovudine on the pharmacokinetics of L-carnitine in rats.