PHAR 4634 - Chapter 16 Page 3

Hemodialysis

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 a semi-permeable 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]:-

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.

Biliary excretion

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