速效抗晕胶囊组分药代动力学相互作用研究

Research on the pharmacokinetic interaction between components of quick-acting anti-motion capsule

目的研究速效抗晕胶囊组分在比格犬体内的单剂量药代动力学及合并用药的相互作用。方法采用自身对照、按随机数字表交叉试验方法，选择三制剂三周期的3—3拉丁方设计，即6只成年、健康比格犬随机分成3组，每组2只。一周期试验3组分别服用速效抗晕胶囊、茶苯海明对照药物和硫酸右旋苯丙胺对照药物，第二周期试验3组分别服用速效抗晕胶囊、硫酸右旋苯丙胺对照药物和茶苯海明对照药物，第三周期试验，3组分别服用硫酸右旋苯丙胺、速效抗晕胶囊复方实验药物与苯海拉明对照药物。每次试验周期间隔7d。采用液相色谱／质谱／质谱（LC／MS／MS）联用方法测定血浆中硫酸右旋苯丙胺和茶苯海明。通过临床前药代动力学研究，分别估算以硫酸右旋苯丙胺和茶苯海明表征的速效抗晕胶囊药物的相对生物利用度和主要药代动力学参数。结果单剂量口服速效抗晕胶囊和硫酸右旋苯丙胺后的药代动力学参数：血药浓度达峰时间[tmax，（2．2±0．4）h和（2，1±0．5）h]、1次给药后最大血药浓度的对数（lnCmax，5．64±0．33和5．74±0．37）、0—24h的血药浓度-时间曲线下面积对数（1nAUC0—24，7．47±0．31和7．49±0．35），差异均无统计学意义（P〉0．05），对lnCmax、／nAUC0—24进行双单侧t检验表明，单用硫酸右旋苯丙胺对照药物20mg及与茶苯海明、速效抗晕胶囊合用时，硫酸右旋苯丙胺的主要药代动力学参数无明显改变（P〉0．05）。单剂量口服给药速效抗晕胶囊和茶苯海明对照药物后的药代动力学参数t。。（2．8±0．4和2．7±0．5）、lnCmax（7．26±0．24和7．33±0．28）、lnAUC0—24（8．65±0．35和8．92±0．41），差异均无统计学意义（P〉0．05），对lnCmax,nAUC0-24进行双单侧t检验表明单用茶苯海明对照药物20mg及速效抗晕胶囊时茶苯海明的主要药代动力学参数无明显改变（P〉0．05）。结论速效抗晕胶囊即硫酸右旋苯丙胺茶苯海明生姜提取物复方药物合并用药不存在明显的药代动力学相互作用。

Objective To study the pharmacokinetics of the quick-acting anti-motion capsules with a single dose in beagle dogs and its interaction, when combined with other drugs. Methods Six adult healthy Beagle dogs were randomly divided into 3 groups, each consisting of 2. The tri-preaparatum and tri-periodieity Latin square method was used in the experiment. During the first phase of the experiment, the animals of the 3 groups were respectively administered the quick-acting anti-motion capsule and the control drugs-- dimenhydrinate and dextroamphetamine sulfate. During the second phase of the experiment, all the animals of the 3 groups were respectively given dimenhydrinate, dextroamphetamine sulfate and the quick-acting anti- motion capsule. During the third phase of the experiment, the animals of the 3 groups were respectively given dextroamphetamine sulfate, the quick-acting anti-motion capsule and dimenhydrinate. Level of dextroamphetamine sulfate and dimenhydrimate in the serum were measured with LC/MS/MS. Through the access of pre-clinical pharmacokinetics studies, we estimated relative bioavailability and main the quick-acting anti-motion capsule pharmacokinetie parameters of, as characterized by dextroamphetamine sulfate and dimenhydrimate. Results No significant differences could be seen in the pharmacokinetic parameters including tmax.lnC /nAUC0-24 following oral administration of a single dose of quick-acting anti-motion capsule and dextroamphetamine（ P 〉 0.05 ）. Two one-sided t tests of the lnCmax and /nAUC0-24 indicated that the pharmacokinetic parameters of dextroamphetamine sulfate combined with dimenhydrimate and the ginger extract （quick-acting anti-motion capsule） do not change distinctly, when compared with those of dimenhydrimate （P 〉 0.05）. Conclusions No significant pharmacokinetic interaction could be noticed, when the components of the ginger extract （quick-acting anti-motion capsules ） were combined with dimenhydrimate and Dextroamphetamine sulfate.