Kozlowski K H, Szaykowski A, Danysz A
Pol J Pharmacol Pharm. 1977 Sep-Oct;29(5):497-508.
Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.
戊巴比妥（PB）在20 - 50毫克/千克的剂量范围内，在兔子身上呈现非线性、剂量依赖性动力学。药物消除的药代动力学参数很大程度上取决于剂量，而分布阶段与剂量无关。PB从中央室（血浆）消失的速率随剂量增加而降低。药效学参数分析表明，PB消除的这种剂量依赖性延迟可能是由循环系统紊乱导致代谢过程受损引起的。已发现PB的降压作用与消除常数k13之间以及降压作用与β.Vd（外推）之间存在密切相关性，β.Vd（外推）是一个与PB代谢速率成比例的系数[23, 29]。结果表明在药代动力学研究中考虑与药物作用相关的机体功能状态变化的必要性。
