Pharmacokinetically Enhanced Protease Inhibitor Combinations
Can exploit drug interactions to enhance/improve therapy:
- Double protease combinations
- Ritonavir boosted regimens
- Delavirdine boosted regimens
Possible outcomes of improving PI kinetics:
- increase antiviral activity
- less frequent/lower dosing, remove food restrictions
- overcome low-level viral resistance
Notes:
- Combining agents from different classes, or even using various agents from similar classes may be desirable, for a number of different reasons:
- To improve antiretroviral pharmacokinetics. Often, the efficacy of an antiretroviral is limited or affected by its disposition in humans. One may sometimes take advantage of enzyme inhibiting properties in order to improve the bioavailability and/or pharmacokinetic profile of one or more drugs.
- To improve adherence. When certain drugs are combined, dosing regimens may be simplified, and often pill burden and/or food restrictions may be minimized. For instance, when indinavir and ritonavir are combined, the dosage of indinavir may be reduced to 400 mg twice daily. In addition, in the presence of ritonavir, indinavir absorption is no longer significantly affected by the presence of food.
- To minimize side effects. The standard dosage of ritonavir is 600 mg twice daily. At this dosage, many patients may experience significant toxicity. When ritonavir is combined with saquinavir, a lower dosage may be used, with better tolerance. Another example may be seen when indinavir is coadministered with ritonavir: indinavir peak levels are lower, which may potentially be associated with a reduced risk of nephrolithiasis.
- To enhance antiviral activity. Additive or synergistic antiviral effects may be observed when various antiretrovirals are administered together.