Definition and mechanisms
A pharmacokinetic booster is an agent that improves the pharmacokinetic properties of another agent. It is a desirable drug interaction It can exert its effects at different levels (ADME):
- Absorption (uptake into the body).
- Distribution (distribution)
- Metabolism and first-pass metabolism (metabolization).
- Elimination (excretion)
Pharmacokinetic enhancers can increase absorption, increase distribution to an organ (e.g., the brain), and inhibit metabolism or elimination. As a result, they increase systemic exposure and thus efficacy, for example. The dose may be reduced or the dosing interval may be extended (e.g., once-daily instead of twice-daily dosing). Pharmacokinetic boosters exploit drug-drug interaction mechanisms. They are predominantly inhibitors of metabolic enzymes (primarily CYP450) and of transporters (e.g., P-glycoprotein, organic anion transporters, OAT). Pharmacokinetic boosters may themselves also be pharmacologically active or inactive. Not all agents are suitable for “boosting,” nor is it necessary for all.
Examples
- Quinidine sulfate, a CYP2D6 inhibitor, is combined with dextromethorphan; see Dextromethorphan and Quinidine Sulfate.
- Cobicistat is a CYP3A inhibitor that is co-administered with HIV medications.
- Decarboxylase inhibitors such as benserazide and carbidopa allow selective metabolism of levodopa to dopamine in the central nervous system.
- Probenecid inhibits the secretion of organic anions and reduces their excretion in the urine at the kidney. It was developed to “stretch” penicillins.
- Ritonavir inhibits CYP3A isozymes and is combined with HIV and HCV drugs.
- Tipiracil inhibits the degradation of the cytostatic drug trifluridine, increasing its bioavailability.
