Design: Three open-label, fixed-sequence drug interaction studies
Population: 54 healthy volunteers (18 per study)
Primary outcome: Aildenafil Cmax and AUC with and without interacting drug
Effect: Clarithromycin AUC ratio 2.58 (2.42–2.76); rifampicin AUC ratio 0.01 (0.01–0.02); cimetidine 1.17

Three fixed-sequence studies in healthy volunteers, published in the British Journal of Clinical Pharmacology (13 September), tested the PDE5 inhibitor aildenafil — cleared mainly by CYP3A4 — with clarithromycin (a strong inhibitor), rifampicin (a strong inducer) and cimetidine, each in 18 people.

Clarithromycin raised aildenafil exposure 2.58-fold by AUC and peak concentration 1.67-fold. Rifampicin reduced AUC to about 1% of baseline and peak to about 2%. Cimetidine had no meaningful effect.

Aildenafil is not widely marketed, but the pattern applies to the class and to many CYP3A4 substrates: a strong inhibitor roughly doubles to triples exposure, and a strong inducer can remove the drug's effect almost entirely. With rifampicin in wide use for tuberculosis in India, that second effect deserves more attention than it gets — co-prescribed CYP3A4 substrates may simply stop working.

Expect strong CYP3A4 inhibitors such as clarithromycin to raise PDE5 inhibitor exposure two- to three-fold.
Assume rifampicin may make CYP3A4 substrates ineffective, not just weaker.
Check every co-prescription for patients starting tuberculosis treatment with rifampicin.
Cimetidine did not meaningfully alter exposure in this study.

Why it matters

Loss of efficacy from induction is quieter than toxicity from inhibition, and is easily missed.

The statistics, in plain English

A geometric mean ratio for AUC of 2.58 means total exposure rose about two and a half times. A ratio of 0.01 means exposure fell to about 1% of what it was — a 99% reduction. These are single-dose studies in healthy volunteers.