Harrison L I, Gibaldi M
J Pharm Sci. 1976 Sep;65(9):1346-8. doi: 10.1002/jps.2600650921.
A two-compartment model representing the body and the GI tract, with elimination occurring in each compartment, was used to study, in theory, the influence of impaired biliary excretion on drug disposition. The results suggest that cholestasis can either increase or decrease a drug's half-life, depending upon the relative values of the two elimination rate constants, In all cases, however, impaired biliary excretion reduced the initial elimination of drug from the body and increased the half-life of the alpha-phase of drug disposition.
采用一个代表机体和胃肠道的二室模型,每个室均有消除过程,从理论上研究胆汁排泄受损对药物处置的影响。结果表明,胆汁淤积可使药物半衰期增加或减少,这取决于两个消除速率常数的相对值。然而,在所有情况下,胆汁排泄受损均会降低药物从体内的初始消除,并增加药物处置α相的半衰期。