Some drugs are excreted into bile and delivered to the intestines. Prior to elimination from the body, the drug may be absorbed. This process is known as:
A. Hepatic clearance.
B. Total clearance.
C. Enterohepatic cycling.
D. First-pass effect.
Correct Answer: C. Enterohepatic cycling.
Drugs and drug metabolites with molecular weights higher than 300 may be excreted via the bile, stored in the gallbladder, delivered to the intestines by the bile duct, and then reabsorbed into the circulation. This process reduces the elimination of drugs and prolongs their half-life and duration of action in the body.
Option A: Hepatic clearance is the amount of drug eliminated by the liver. Hepatic drug clearance can be defined as the volume of blood perfusing the liver that is cleared of the drug per unit of time. There are three major parameters that determine drug elimination by the liver: blood flow through the liver (Q), which reflects drug delivery to the liver.
Option B: Total clearance is the sum of all types of clearance including renal, hepatic, and respiratory. Clearance is the parameter that determines total systemic exposure to drugs, which is simply the ratio of dose/clearance. Total body clearance is the sum of all processes by which drugs are removed from the body or inactivated, primarily renal excretion and metabolism.
Option D: First-pass effect is the amount of drug absorbed from the GI tract and then metabolized by the liver; thus, reducing the amount of drug making it into circulation. The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation. The first pass effect is often associated with the liver, as this is a major site of drug metabolism. However, the first pass effect can also occur in the lungs, vasculature, gastrointestinal tract, and other metabolically active tissues in the body.