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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。
Objective To study the effect of zidovudine on the level of endogenous L-carnitine and pharmacokinetics of levocarnitine in rats. Methods 18 Wistar rats were randomly divided into A, B, C 3 groups. Group A was blank control group, not given; group B was given zidovudine alone; group C was given zidovudine and levocarnitine. Continuous administration for 45 days, LC-MS / MS method was used to determine and compare endogenous L-carnitine levels in muscle and heart of rats in each group. Twelve Wistar rats were randomly divided into two groups, one was given levocarnitine, and the other was given levocarnitine and zidovudine. The rats in two groups were determined by LC-MS / MS Pharmacokinetics of levocarnitine after drug concentration changes over time, with the DAS 2.1.1 software to calculate the main pharmacokinetic parameters, and statistical analysis and comparison. Results After long-term administration of zidovudine in rats, levocarnitine level in muscle was significantly lower than that in control group, and there was no significant change in left carnitine level in heart. After administration of zidovudine and levocarnitine, rats There was no significant difference in levocarnitine level between the two groups in comparison with the control group, and the levocarnitine level in the heart was significantly increased. There was no significant difference in the main pharmacokinetic parameters between rats given levocarnitine and zidovudine and levocarnitine. Conclusion Zidovudine can inhibit the uptake of levocarnitine in muscle tissue. Supplementing L-carnitine while treating zidovudine can relieve the adverse reactions induced by zidovudine. Carnitine pharmacokinetics no significant effect.