DEPENDENCE OF PENTOBARBITAL KINETICS UPON DOSE OF DRUG AND ITS PHARMACODYNAMIC EFFECTS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 29  (5) , 497-508
Abstract
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 shows 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 was found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and .beta. .cntdot. Vd(extrap), a coefficient proportional to the rate of metabolism of PB. The changes in the functional state of the organism, related to the action of a drug, must be considered in pharmacokinetic studies.