Arteriovenous serum cocaine concentration difference after intravenous bolus injection and constant-rate infusions: relation to pharmacodynamic estimates in rats.
Arteriovenous serum cocaine concentration difference after intravenous bolus injection and constant-rate infusions: relation to pharmacodynamic estimates in rats.
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DOI：
10.1016/s0928-0987(01)00180-4
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发表时间：
2001-12
期刊：
影响因子：
--
通讯作者：
L. Sun;C. Lau
中科院分区：
文献类型：
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作者：
L. Sun;C. Lau
我们使用大鼠推注剂量（2 mg/kg）和两次恒速输注（12.24和24.48 μg/min）2 h后的动脉和静脉血清数据表征可卡因的药代动力学。使用已发表的行为效应研究动静脉血清浓度差异对2 mg/kg剂量药效学估计值的影响。显着的时间动静脉血清可卡因和苯甲酰芽子碱（主要代谢产物）的浓度差异存在可卡因管理后。动脉血清数据的AUC大于静脉数据的AUC，表明可卡因在静脉采样部位代谢更广泛。考马斯亮蓝的行为效应可能与血清浓度直接相关，在效应与动脉或静脉血清浓度之间没有观察到滞后。从动脉血清数据得出的药效学估计值与从静脉数据得出的药效学估计值近似，因为可卡因效应的最大下降发生在消除期，在此期间，两个采样部位之间的血清可卡因浓度没有显著差异。
We characterized the pharmacokinetics of cocaine using both arterial and venous serum data after a bolus dose (2 mg/kg) and two constant-rate infusions (12.24 and 24.48 μg/min) for 2 h in rats. A published behavioral effect was used to investigate the effects of arteriovenous serum concentration differences on pharmacodynamic estimates for the 2 mg/kg dose. Significant temporal arteriovenous serum cocaine and benzoylecgonine (the major metabolite) concentration differences existed after cocaine administrations. The AUCs for arterial serum data were greater than the AUCs for venous data, indicating that cocaine was metabolized more extensively in the venous sampling site. Cocaine’s behavioral effect could be directly related to serum concentrations with no hysteresis observed between the effects and arterial or venous serum concentrations. The pharmacodynamic estimates derived from arterial serum data approximated those from the venous data due to the most decline of cocaine’s effect occurred in the elimination phase during which serum cocaine concentrations were not significantly different between the two sampling sites.