A woman taking an oral contraceptive starts rifampicin therapy for latent tuberculosis and becomes pregnant despite good compliance. Why does loss of contraceptive effect typically take several days to become fully manifest after starting rifampicin, whereas loss of effect from a strong CYP inhibitor appears within hours?

• A Rifampicin must first accumulate to high plasma concentrations before acting
• B Enzyme induction requires transcription of new cytochrome protein, a slow process ✓
• C Oral contraceptives have a long half-life that delays the interaction
• D Rifampicin induces enzymes only after hepatic biotransformation to an active metabolite

Explanation

Rifampicin activates nuclear receptors such as PXR, increasing transcription of CYP genes; synthesis of new enzyme protein means induction builds over days and persists for weeks after stopping. Competitive or mechanism-based inhibition, in contrast, acts on existing enzyme molecules and appears within hours to days. The delay therefore reflects the biology of gene expression, not drug accumulation or metabolite formation.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

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Written and medically reviewed by the StethoPrep medical team.