Complexity and clinical significance of drug–drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT)

Table 1 Types of drug–drug interactions (DDIs)

Type of DDIs	Main proteins involved	Mechanisms
Pharmacodynamic interactions	-	Additive effects of the two drugs
Drug transporter DDIs	BCRP, OATP, OCT, MATE, OATP, P-gp	Inhibition of the transporter leads to a higher drug blood concentration Induction of the transporter leads to a lower drug blood concentration
Pharmacokinetic interactions	CYP3A4 (mainly), CYP2C9,…	Inhibition of the CYP3A4 leads to a higher drug blood concentration Induction of the CYP3A4 leads to a lower drug blood concentration
Human plasma protein DDIs	Albumin, alpha 1-glycoprotein	Competition on the binding site of a protein carrier change the drug concentration because only the free drug is active
Absorption DDIs	-	Intragastric pH influences the solubility and bioavailability of drugs

BCRP: breast cancer resistance protein; DDIs: drug–drug interactions; MATE: multi-antimicrobial extrusion protein; OAT: organic anion transporters; OCT: organic cation transporters; P-gp: P-glycoprotein