VPT 311: General and Systemic Veterinary Pharmacology (2+1)

HEPATIC AND OTHER ROUTES OF ELIMINATION

Hepatic elimination of drugs

• Hepatically eliminated drugs usually move by passive diffusion from the blood into the hepatocyte from where they are secreted into the bile or metabolised first and then secreted into the bile.
• The bile then conveys this to the duodenum. In acute liver diseases and in chronic degenerative processes like cirrhosis, the liver’s ability to metabolise and/or eliminate drugs is reduced. Therefore the dose of the drugs eliminated by liver must be reduced in liver disorders in order to prevent drug accumulation in toxic concentrations.
• Choleretics or a high fat intake promote bile flow and therefore, biliary excretion and enhance the hepatic secretion of drugs. Broad spectrum antibacterial agents are expected to diminish the hydrolytic action of intestinal flora and thus, may prevent effective enterohepatic cycles.
• Large polar molecules (molecular weight >300) are often excreted and are not reabsorbed in the intestine.
• The ability to excrete polar compounds in bile with molecular weights between 300 and 500 is good in dog, chicken and rat, moderate in cat and sheep and poor in guinea pig, rabbit, monkey and man.

Compounds that undergo biliary excretion

Unchanged drugs and endogenous substances	Compounds excreted as glucuronide conjugates
Erythromycin	Chloramphenicol
Clindamycin	Trimethoprim
Digitoxin	Sulphadimethoxine
Steroid hormones	Morhine

Excretion of drugs in milk

• This route of excretion has both therapeutic and public health importance.
• The principles of excretion through the mammary gland are similar to those acting in the kidneys, namely the diffusion of unionised lipid soluble forms of the drugs diffusing through the epithelial cells of the mammary gland.
• The pH of plasma and milk are important factors. Since milk is usually more acidic than plasma the basic compounds may be slightly more concentrated and acidic compounds are less concentrated in milk than plasma.
• Excretion of drugs is altered in cases of mastitis due to changes in the pH of milk.