Slide 30 of 76
Notes:
- Ritonavir has extremely potent inhibitory effects on the cytochrome P450 system. Agents such as indinavir, nelfinavir, amprenavir, and delavirdine have moderate inhibitory effects, while saquinavir is a weak inhibiting agent.
- Therefore, of the currently available protease inhibitors and NNRTIs, ritonavir would be expected to have the most pronounced effect on the metabolism of cytochrome P450 substrates, and consequently may be associated with more potentially significant interactions.
- For example, different protease inhibitors have different effects on saquinavir metabolism:
- SQV + indinavir: 620% increase in SQV-soft gel capule AUC; no apparent clinically relevant changes to IDV
- SQV + nelfinavir: 392% increase in SQV-soft gel capsule AUC (similar effect observed with SQV-hgc plus NFV); may use lower dose of SQV-SGC (i.e., 800 mg vs. 1200 mg TID).
- SQV + ritonavir: 50- to 100-fold increase in SQV AUC. Regimen of SQV 400 mg BID and RTV 400 mg BID well tolerated.
