Godley P J, Moore E S, Woodworth J R, Fineg J
University of Texas, Austin.
Biopharm Drug Dispos. 1991 Apr;12(3):189-99. doi: 10.1002/bdd.2510120303.
A three-way crossover study was performed to determine the influence of delta 9-tetrahydrocannabinol (THC) and ethanol (EtOH) separately upon phencyclidine (PCP) disposition in dogs. Seven dogs were given three single dose treatments: 1.5 mg PCP kg-1 i.v., 1.5 mg PCP kg-1 i.v. with 0.4 mg kg-1 THC i.v., and 1.5 mg PCP kg-1 i.v. with 1.25 g EtOH kg-1 i.v. PCP was measured in plasma samples collected for 24 h after administration of each treatment, with several pharmacokinetic parameters calculated from the plasma concentration vs time data. The PCP serum Cls values were significant change in V beta or t1/2. EtOH did not induce significant changes in any PCP pharmacokinetic parameter, although mean Cls and V beta were increased. These results confirm the observed THC inhibition of PCP metabolism, and suggest that the enhanced pharmacologic action of PCP by THC may result from higher serum PCP concentrations. These results further suggest that enhanced PCP actions by acute EtOH administration may result from increased PCP distribution to the CNS.
进行了一项三向交叉研究，以确定δ9-四氢大麻酚（THC）和乙醇（EtOH）分别对犬体内苯环己哌啶（PCP）处置的影响。七只犬接受了三种单剂量治疗：静脉注射1.5mg/kg的PCP、静脉注射1.5mg/kg的PCP并同时静脉注射0.4mg/kg的THC、静脉注射1.5mg/kg的PCP并同时静脉注射1.25g/kg的EtOH。在每次给药后收集24小时的血浆样本以测量PCP，并根据血浆浓度与时间数据计算几个药代动力学参数。PCP的血清清除率（Cls）值在Vβ或t1/2方面有显著变化。EtOH并未引起任何PCP药代动力学参数的显著变化，尽管平均Cls和Vβ有所增加。这些结果证实了观察到的THC对PCP代谢的抑制作用，并表明THC增强PCP的药理作用可能是由于血清中PCP浓度较高所致。这些结果进一步表明，急性给予EtOH增强PCP作用可能是由于PCP向中枢神经系统的分布增加所致。
