What question did this study set out to answer?

To evaluate the capacity of efavirenz to induce hepatic CYP3A4, intestinal CYP3A4, and intestinal P-glycoprotein across two different daily doses in healthy volunteers.

July 1, 2002Clinical Pharmacology & TherapeuticsOpen Access

Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans

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To evaluate the capacity of efavirenz to induce hepatic CYP3A4, intestinal CYP3A4, and intestinal P-glycoprotein across two different daily doses in healthy volunteers.
Randomized (2:1) placebo-controlled trial in two cohorts of 12 healthy subjects receiving either daily oral efavirenz (200 mg or 400 mg) or placebo for 10 days.
Hepatic CYP3A4 activity was assessed on 9 occasions using the erythromycin breath test (ERMBT), while intestinal CYP3A4 and P-glycoprotein levels were measured by immunoblotting of pre- and post-treatment intestinal biopsy specimens.
Plasma efavirenz concentrations were determined using HPLC to evaluate pharmacokinetic parameters by noncompartmental methods.
Efavirenz produced a significant dose- and time-dependent increase in hepatic CYP3A4 activity, causing a mean induction of 33% at 200 mg and 55% at 400 mg compared with placebo (P < .01 for each).
Systemic drug exposure (AUC on day 10) correlated significantly with the magnitude of liver CYP3A4 induction across combined dose groups (r = 0.509; P = .04).
Efavirenz administration had no detectable effect on intestinal CYP3A4 or intestinal P-glycoprotein expression.

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Implication

Randomized placebo-controlled trial shows efavirenz induces liver CYP3A4 dose-dependently without altering intestinal CYP3A4 in healthy volunteers, indicating tissue-specific drug interactions.

Cite This Study

Mouly et al. (2002) studied this question.

synapsesocial.com/papers/6a8798fe4845184cc7a29e4d https://doi.org/10.1067/mcp.2002.124519

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Implication

Randomized placebo-controlled trial shows efavirenz induces liver CYP3A4 dose-dependently without altering intestinal CYP3A4 in healthy volunteers, indicating tissue-specific drug interactions.

Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans

Key Points

Discussion

Implication

Cite This Study

Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans

Key Points

Discussion

Implication

Cite This Study

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