Relation between renal and hepatic excretion of drugs: I. Phenol red in comparison with p-aminohippurate and indocyanine green.

Phenol red is a suitable compound for the simultaneous assay of renal and hepatic excretion in the rat. Its elimination has been compared with those of p-aminohippurate (PAH) and indocyanine green (ICG) which are eliminated nearly exclusively via kidneys or liver, respectively. The interruption of one elimination route one day before the experiment, that means bile duct ligation (DL) in the case of ICG or bilateral nephrectomy (NX) in the case of PAH are followed by a slight increase in the elimination via the alternative pathway, but no effective compensation occurs. On the other hand, the renal excretion of phenol red is significantly increased after DL only following administration of high doses. This intensification is caused by an increase in the unbound amount of phenol red depending on the plasma concentration and reflects an enhanced glomerular filtration fraction. The biliary excretion increases significantly after NX, but only after infusion of low doses. The maximal biliary secretion capacity cannot be exceeded following NX, either. The competitive inhibition of phenol red excretion by probenecid supports the findings of NX or DL experiments. An influence of the three test substances on arterial blood pressure has been excluded. The most important factors influencing the switch over from one to the other elimination route seem to be at least in the case of phenol red the amount of unbound substance, the influence of the administered dose on the glomerular filtration, and disturbances in the volume of distribution, e.g. the possible reduction of hepatic uptake after DL.