ABSTRACT
Conjugations are ubiquitous among drug-eliminating organs and require the presence of both the transferases and co-substrates. Generally speaking, the liver is the most important organ involved in the conjugation of xenobiotics, though demonstrable lung (Cassidy and Houston, 1984), intestine (Barr and Riegelman, 1970; Dollery et al., 1971; Bock and Winne, 1975; Pinkus et al., 1977; Shibasaki et al., 1981), kidney (Tremaine et al., 1984) and skin (Pannather et al., 1978) conjugation abilities have also been reported. To adequately address the topic of conjugation kinetics in any eliminating organ, consideration must be given to the factors which influence drug and metabolite clearances. These include the blood perfusion rate to the organ, the transport process for the conjugate and its precursor, the extent of binding to blood (red cell and plasma proteins) components, availability of conjugative enzymes and co-substrate, the enzymic parameters and attendant zonal heterogeneity, the presence of other competing pathways and whether the formed metabolite is subject to further metabolism (Pang and Xu, 1988). The functional heterogeneities of the organ (Gumucio and Miller, 1978), notably, zonation of enzymes, is the most prominent factor.
