PHAR 4634 - Chapter 16 Page 3
Hemodialysis or `artificial kidney' therapy is used in renal failure to remove
toxic waste material normally removed by the kidneys, from the patient's
blood. In the procedure blood is diverted externally and allowed to flow across
membrane that is bathed with an aqueous isotonic solution. Nitrogenous waste
products and some drugs will diffuse from the blood, thus these compounds will
be eliminated. Therefore in patients with kidney failure, hemodialysis will be
an important route of drug elimination.
This technique is particularly important with drugs which:-
1) have good water solubility;
2) are not tightly bound to plasma protein;
3) are smaller (less than 500) molecular weight; and
4) have a small apparent volume of distribution.
Conversely drugs which are tightly bound or extensively stored or distributed
into tissues are only poorly removed by this route, or process.
The liver secretes 0.25 to 1 liter of bile each day. Some drugs and their
metabolites are excreted by the liver into bile. Anions, cations, and non-ionized
molecules containing both polar and lipophilic groups are excreted into the
bile provided that the molecular weight is greater than about 300. Molecular
weights around 500 appears optimal for biliary excretion in humans. Lower
molecular weight compounds are reabsorbed before being excreted from the bile
duct. Conjugates, glucuronides (drug metabolites) are often of sufficient
molecular weight for biliary excretion. This can lead to biliary recycling.
Indomethacin is one compound which undergoes this form of recycling.
Diagram XVI-2 Enteroheptic Recycling
Figure XVI-1 Cp versus Time showing a Second Peak
Other compounds extensively excreted in bile include cromoglycate (unchanged
drug), morphine, and chloramphenicol (as glucuronide). At least part of the
biliary secretion is active since bile/plasma concentrations maybe as high as
50/1. There can also be competition between compounds.
The efficiency of this biliary excretion system can be assessed by use of a
test substance, such as Bromsulphalein.
This page was last modified: 12 February 2001
Copyright 2001 David W.A. Bourne