Piotrovskiĭ V K, Shvachko E V, Trnovec T
Eksp Klin Farmakol. 1994 Sep-Oct;57(5):37-40.
A physiological perfusion pharmacokinetic model was used to assess the possible differences in the model-independent pharmacokinetic parameters of drug enantiomers (total clearance, mean retention time, half-life and stationary distribution volume), depending on differences in their blood binding and in the values of intrinsic hepatic clearance. The distribution in the organs and tissues and renal clearance of enantiomers were assumed to be equal. The maximally possible values of the relationships of the above parameters were found for enantiomers. The relative values of parameters vary irregularly with the increase in the values of intrinsic hepatic clearance: drastic changes occur in the range 0 to 100 liter/hour, but they do not take place in the range 100 to 1000 liter/hour. The differences in enantiomeric parameters also decrease as the blood binding of enantiomers drops.
采用生理灌注药代动力学模型,根据对映体的血液结合差异和肝内在清除率值,评估对映体在非模型依赖药代动力学参数(总清除率、平均滞留时间、半衰期和稳态分布容积)方面可能存在的差异。假定对映体在各器官和组织中的分布以及肾清除率相等。确定了对映体上述参数关系的最大可能值。参数的相对值随肝内在清除率值的增加而不规则变化:在0至100升/小时范围内发生剧烈变化,但在100至1000升/小时范围内则不发生变化。对映体参数的差异也随着对映体血液结合率的下降而减小。