As we develop drugs to be more stable in our body (i.e. less prone to be broken down by liver), guess what is another route that the drugs are being eliminated from our body?
It is intestinal excretion of drugs from the blood circulation to the intestinal lumen and out of our body via feces!
One example is a blood thinning drug known as apixaban where more than half of it is being intestinally excreted and recovered in the feces as unchanged parent drug!
The remaining half of apixaban is removed from our body via excretion in the kidney and breaking down in liver.
A question arises: Can the clearance of apixaban by intestinal excretion (ClI) be added to its clearance in the liver and kidney (CLR and CLH, respectively)?
As a recap, in the absence of CLI, we add CLR to CLH to calculate total clearance (CL) because the blood concentration level of drug entering the kidney and liver is the same (i.e. these organs are arranged in parallel).
However, in the presence of major CLI, the blood concentration level of drug entering the liver is in principle lower than that entering the intestine and kidney (see figure below).
Hence, while CLI may be added to CLR, the same cannot be applied to CLH. In other words, it may be inaccurate to write the following equation (which appears in some literature).
Total clearance, CL = Hepatic clearance, CLH + Renal clearance, CLR + Intestinal clearance, CLI
To model CL, we may apply dynamic modeling method such as physiologically based pharmacokinetic (PBPK) modelling.
Back to apixaban, what are the implications of its intestinal excretion?
- As apixaban is excreted in the intestine by transporters, concomitant drugs or food substances that block these intestinal transporters may increase the blood levels of apixaban leading to potential bleeding risk.
- When activated charcoal is taken with apixaban (i.e. treatment of food poisoning or diarrhea), the intestinal clearance of apixaban increases, leading to decreased blood levels of apixaban and risk of clotting.
Read also: Concepts of Elimination Rate and Clearance of Drugs
Resource Person: Eric Chan, PhD