Table 3.

Effect on targeted drug pharmacokinetics by CYP3A4 Inhibition and Induction

Drug	Pharmacokinetic Change in Drug Levels (AUC) (%)
	Inhibitor	Inducer
Imatinib	40	-380 (RMP)
Dasatinib	500	- 82 (RMP)
Nilotinib	300	- 80 (RPC)
Erlotinib	67	- 67 to - 80 (RPC)
Sunitinib	51	- 46 (RMP)
Lapatinib	360	- 72 (CBZ)
Bortezomib	35	n/a
Sorafenib	0	-37 (RPC)
Temsirolimus	310 *	-56 * (RMP)

Percent change in pharmacokinetics of targeted agents as measured by Area Under Concentration (AUC) curve by the co-administration of drugs known to inhibit or induce the CYP3A4 metabolizing enzyme. A CYP3A4 inhibitor prevents metabolism of the drug and leads to higher serum drug levels as reflected in drug AUC, whereas an enzyme inducer would lead to decreased blood levels. Ketoconazole was used as the inhibiting agent, whereas rifampin (RMP), rifampicin (RPC), or carbamazepine (CBZ) were used as inducing agents. References and discussion are included in the text.

^*For temsirolimus, the parent drug was unaffected but the active metabolite sirolimus was affected by the inhibiting and inducing agents.