ABSTRACT
The process of urine formation and xenobiotic excretion begins with the passage of blood through the glomerulus to yield a tubular fluid which is essentially an ultrafiltrate of plasma. Protein binding is a major limitation in glomerular filtration of xenobiotics since it diminishes the free drug concentration gradient across the capillary membrane. Excretion of methotrexate, an organic anion, is inhibited by salicylates which compete for tubular transport. This important drug interaction may lead to toxic blood levels of the antitumor agent. Biliary excretion has frequently been studied from the viewpoint of movement from plasma to bile, overlooking the distinction between hepatic uptake and canalicular transport. Most xenobiotics are converted to metabolites prior to excretion in bile or urine. Administration of nafenopin increases liver size and evokes a marked choleresis accompanied by inhibition of biliary excretion of organic anions and uncharged xenobiotics, but not organic cations.
