Interaction study of ketoconazole and ritonavir-boosted saquinavir
This study investigated the steady state pharmacokinetics of saquinavir, ritonavir and ketoconazole in healthy subjects receiving saquinavir/ritonavir (1000/100 mg twice daily) and ketoconazole (200 mg once daily) alone and in combination.
Coadministration had no clinically significant effect on the AUC or Cmax of saquinavir (7% and 2% increases, respectively) or ritonavir (12% and 8% increases respectively). However, the AUC of ketoconazole increased by 2.68-fold and Cmax increased by1.45-fold. Ketoconazole half life increased from 4.3 h to 10.7 h and CL/F decreased by more than 50% (from 8.22 to 3.07 L/h).
In this study the increase in ketoconazole exposure with saquinavir/ritonavir was not associated with unacceptable safety or tolerability. No dose adjustment of saquinavir or ritonavir is required when administered with doses of ketoconazole of 200 mg/day or lower. Based on the hepatotoxicity liability of ketoconazole, high doses (>200 mg/day) are not recommended.
Kaeser B et al. Drug-drug interaction study of ketoconazole and ritonavir-boosted saquinavir. Antimicrob Agents Chemother, 2009, 53(2): 609-614.