Relation between renal and hepatic excretion of drugs: II. Age-dependence of phenol red excretion in comparison with those of p-aminohippurate and indocyanine green

Abstract

The excretory functions of kidney and liver do not develop simultaneously during the maturation of an individual. Therefore age related differences in the relation between renal and hepatic drug excretion could be expected. In this study the excretion of p-aminohippurate (PAH) and indocyanine green (ICG) as model substances for nearly exclusive excretion via kidney or liver, respectively, have been compared with that of phenol red eliminated both via kidneys and liver (3:1). Experiments were performed on rats between the 10th and 105th days of life. For PAH and ICG the typical age courses of renal or hepatic excretion have been confirmed. Both urinary and biliary phenol red excretion show an influence of age, however, renal elimination reaches adult values as early as at the 20th day of life. Furthermore the age relation concerning compensation of the loss of kidney or liver excretory functions has been studied. Neither after nephrectomy (NX) nor after bile duct ligation (DL) the PAH or ICG elimination via the alternative pathway, respectively, were quantitatively increased. Thus a compensation of the interruption of the main elimination route does not occur in all ages. In contrast, phenol red excretion into urine and bile increases distinctly after DL or NX. This increase becomes even significant after administration of suitable doses of phenol red saturating transport capacities of liver or kidney. The compensation is first of all caused by passive pharmacokinetic changes. Active compensatory mechanisms have not been proved.