Rifampicin is a powerful enzyme inducer. It is most likely to induce the metabolism of which of the following anti-retroviral drugs?
**Core Concept**
Rifampicin is a potent cytochrome P450 enzyme inducer, particularly affecting the CYP3A4 isoenzyme. This induction leads to increased metabolism of various drugs, including antiretroviral agents.
**Why the Correct Answer is Right**
The metabolism of antiretroviral drugs, such as protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs), is significantly influenced by the CYP3A4 enzyme. Rifampicin's induction of CYP3A4 results in increased metabolism of these drugs, potentially leading to reduced plasma concentrations and decreased efficacy. This is particularly concerning for protease inhibitors like saquinavir, which are primarily metabolized by CYP3A4. Rifampicin's induction of this enzyme can lead to significant reductions in saquinavir plasma levels.
**Why Each Wrong Option is Incorrect**
**Option A:** Atazanavir is primarily metabolized by CYP3A4, but it is also a substrate of CYP3A5. Rifampicin's induction of CYP3A4 may affect atazanavir metabolism, but the effect is less pronounced compared to protease inhibitors like saquinavir.
**Option B:** Efavirenz is primarily metabolized by CYP2B6 and CYP3A4, but it is not as significantly affected by rifampicin's induction of CYP3A4.
**Option C:** This option is not a valid antiretroviral drug.
**Clinical Pearl / High-Yield Fact**
When initiating rifampicin in HIV-positive patients, it is essential to adjust the dosages of protease inhibitors and monitor plasma concentrations to prevent subtherapeutic levels and treatment failure.
**Correct Answer:** C. Saquinavir.