Boisse N R, Okamoto M
J Pharmacol Exp Ther. 1978 Mar;204(3):526-40.
The withdrawal characteristics of barbital and pentobarbital after "chronically equivalent" treatment suggested that the longer acting barbital was less liable to produce physical dependence. Therefore, to distinguish this potential pharmacodynamic difference from the known pharmacokinetic differences between the two drugs, the rate of elimination of each was adjusted to mimic that of the other. The rate of barbiturate elimination after chronically equivalent pentobarbital dosing was reduced by barbital substitution or by first-order pentobarbital dose reduction, with the result that withdrawal signs became mild and appeared later (3 days postdrug). The rate of barbiturate elimination after chronically equivalent barbital dosing was increased by pentobarbital substitution or by peritoneal dialysis of barbital, with the result that withdrawal signs became severe and appeared sooner (within 1 day). These findings conclusively support the key role of the rate of barbiturate elimination to expose underlying physical dependence to barbiturates. Furthermore, "physical dependence" and its expression in "withdrawal" must be regarded separately to evaluate and compare critically the dependence capability of different drugs.
“长期等效”治疗后巴比妥和戊巴比妥的戒断特征表明，作用时间较长的巴比妥产生身体依赖性的可能性较小。因此，为了将这种潜在的药效学差异与两种药物已知的药代动力学差异区分开来，对每种药物的消除速率进行了调整，使其与另一种药物相似。在长期等效的戊巴比妥给药后，通过巴比妥替代或一级戊巴比妥剂量减少来降低巴比妥酸盐的消除速率，结果戒断症状变得轻微且出现较晚（停药后3天）。在长期等效的巴比妥给药后，通过戊巴比妥替代或巴比妥的腹膜透析来提高巴比妥酸盐的消除速率，结果戒断症状变得严重且出现较早（1天内）。这些发现确凿地支持了巴比妥酸盐消除速率在暴露对巴比妥酸盐潜在身体依赖性方面的关键作用。此外，“身体依赖性”及其在“戒断”中的表现必须分开看待，以便批判性地评估和比较不同药物的依赖能力。
