Imatinib pharmacokinetics alone and in combination with ritonavir (600 mg once daily for 3 days) were evaluated in 11 cancer patients receiving imatinib for at least 2 months (400-800 mg). The dose of imatinib was decreased by 50% during coadministration with ritonavir (for safety reasons) and pharmacokinetic parameters were normalised to an imatinib dose of 400 mg. Coadministration had no significant effect on imatinib AUC or Cmax (decreases of 3% and 13%, respectively). However, plasma exposure of CGP74588 (an active metabolite) was increased by approximately 40%. A population analysis with a time-dependent covariate confirmed that ritonavir did not influence the clearance or bioavailability of imatinib. The authors suggest that at steady state imatinib is insensitive to acute CYP3A4 inhibition by ritonavir and relies on alternate elimination pathways.
Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib. van Erp NP, Gelderblom H, Karlsson MO et al. Clin Cancer Res, 2007, 13(24): 7394-7400.