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In vitro data indicate that cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of apatinib. Pharmacokinetic drug\u2013drug interactions of apatinib and (1) a CYP3A4 inducer (rifampin) or (2) a CYP3A inhibitor (itraconazole) were clinically evaluated in healthy volunteers. Compared with the single administration of apatinib, its coadministration with rifampin resulted in a 5.6\u2010fold plasma clearance (CL\/F) and 83% decrease in plasma AUC<jats:sub>0\u2013t<\/jats:sub> of apatinib. By contrast, coadministration with itraconazole reduced the CL\/F of apatinib by 40% and increased its AUC<jats:sub>0\u2013t<\/jats:sub> by 75%. In summary, a strong CYP3A4 inducer (rifampin) had a strong effect (&gt;5\u2010fold) on the clinical pharmacokinetics of apatinib, whereas a strong CYP3A inhibitor (itraconazole 100 mg once a day) had a weak effect (1.25\u2010 to 2\u2010fold). 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