Alprazolam, caffeine and their interaction: relating DRL performance to pharmacokinetics.
Alprazolam, caffeine and their interaction: relating DRL performance to pharmacokinetics.
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阿普唑仑、咖啡因及其相互作用：将 DRL 性能与药代动力学联系起来。
DOI：
10.1007/bf02246346
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发表时间：
1996
影响因子：
3.4
通讯作者：
Wang,J
中科院分区：
文献类型：
--
作者：
Lau,CE;Wang,J
大鼠低速行为（DRL 45-s）的三小时差异强化课程用于研究阿普唑仑、咖啡因以及它们在血清阿普唑仑开始、达到峰值和消失时的相互作用，同时咖啡因水平保持恒定。 Pöch 的剂量反应曲线 (DRC) 方法允许对组合药物作用中发生的相互作用的类型（相加性或独立性）进行广泛的评估。阿普唑仑和咖啡因 DRC 用于推导理论加法关系和独立关系，以及与这些函数相比观察到的组合效应。类似地比较了组合效应的行为-时间曲线。血清阿普唑仑和咖啡因浓度与其各自的行为时间曲线相关。对于单个药物或其组合，没有观察到急性耐受性。阿普唑仑在破坏 DRL 行为方面比咖啡因更有效。由于阿普唑仑在大鼠体内的作用时间（t1/2=32 分钟）比咖啡因（t1/2=3 小时）短得多，因此阿普唑仑和咖啡因之间的效价比在整个疗程期间发生变化（从 123 到 4），这决定了组合效应的表达。尽管在 DRC 和行为时间曲线中，组合效应在可加性或独立性方面无法区分，但它们既没有表现出协同作用，也没有表现出拮抗作用。咖啡因不会改变阿普唑仑的药代动力学，但阿普唑仑会影响咖啡因的药代动力学。
Three-hour sessions of differential reinforcement of low-rate behavior (DRL 45-s) in rats were used to investigate alprazolam, caffeine, and their interactions at the onset, peak and disappearance of serum alprazolam, while caffeine level remained constant. The dose-response curve (DRC) method of Pöch permitted an extensive evaluation of the kind (additivity or independence) of interactions occurring in combined drug effects. The alprazolam and caffeine DRCs were used to derive theoretical additive and independent relations, and the observed combined effects compared to these functions. Behavior-time profiles of the combined effects were similarly compared. Serum alprazolam and caffeine concentrations correlated with their respective behavior-time profiles. No acute tolerance was observed either for the individual drugs or their combinations. Alprazolam was more potent than caffeine in disrupting DRL behavior. Because alprazolam is much shorter-lived (t1/2=32 min) than caffeine (t1/2=3 h) in rats, potency ratios between alprazolam and caffeine changed across session time (from 123 to 4), which determined the expression of the combined effects. Although the combined effects were not distinguishable in terms of additivity or independence in both the DRCs and in the behavior-time profiles, they showed neither synergism nor antagonism. The pharmacokinetics of alprazolam were not altered by caffeine, but those of caffeine were affected by alprazolam.