Alfentanil is a potent, short-acting analgesic drug used for anesthesia in surgery.
When alfentanil is administered to patients who were pre-treated with rifampin, an anti-tuberculosis drug, its level in our body (i.e. systemic exposure), was reduced 2- to 3-fold!
A question arises: What are the rationales behind this interaction?
- Alfentanil is mainly eliminated in the liver by an enzyme known as CYP3A4.
- Rifampin is a potent inducer of CYP3A4 where it increases its level in the liver.
- While alfentanil is eliminated by CYP3A4, the process is relatively ‘sluggish’ (i.e. low hepatic extraction ratio).
- Consequently, the efficiency of the liver in eliminating alfentanil (i.e. its hepatic blood clearance) is dependent on how CYP3A4 handles alfentanil (i.e. change in its intrinsic clearance).
- When patients are pre-treated with rifampin, level of CYP3A4 increases (i.e. intrinsic clearance increases), elimination efficiency of alfentanil in liver increases (i.e. hepatic blood clearance increases), the level of alfentanil in our body decreases (i.e. systemic exposure decreases) and hence, its effectiveness in anesthesia reduces!
Another question arises: What is the clinical implication?
Patients who are suffering from tuberculosis and taking rifampin for a period of time will need to inform other physicians or pharmacists before being prescribed a new medication.
If interaction occurs as described above, the new medication may not be effective based on contemporary dosing regimen!
Read also: Food-Drug Interactions on Drug Safety & Efficacy
Resource Person: Eric Chan, PhD