- 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 CYP3A modulators
- Effect
- AUC ratio 2.58 with clarithromycin, 0.01 with rifampicin, 1.17 with cimetidine
Three open-label, fixed-sequence studies in 54 healthy volunteers tested aildenafil, a PDE5 inhibitor metabolised mainly by CYP3A4, with three CYP3A modulators.
Clarithromycin, a strong CYP3A4 inhibitor, raised the area under the concentration curve 2.58-fold and peak concentration 1.67-fold. Rifampicin, a strong inducer, reduced exposure to about 1% of baseline (AUC ratio 0.01). Cimetidine, a weak inhibitor, had little effect (AUC ratio 1.17).
Aildenafil is not widely available outside China, but the pattern applies to every PDE5 inhibitor and to many CYP3A4 substrates. A strong inducer can make a drug effectively absent; a strong inhibitor can more than double exposure. Rifampicin, carbamazepine, phenytoin and St John's wort are the inducers most likely to be missed in a medication history.
- Assume rifampicin will make most CYP3A4-metabolised drugs ineffective; check before co-prescribing.
- With clarithromycin or other strong CYP3A4 inhibitors, reduce PDE5 inhibitor doses and warn about hypotension.
- Cimetidine had little effect on exposure in this study.
- Ask about St John's wort and anticonvulsants when a CYP3A4 substrate seems not to work.
- Induction takes days to develop and to wear off after stopping the inducer.
Why it matters
Interactions of this size turn a normal dose into an overdose or a placebo, and they are predictable from the metabolic pathway.
Don't overread it
Single-dose studies in healthy volunteers measure exposure, not clinical effect.
The statistics, in plain English
A geometric mean ratio of 2.58 means exposure was about 2.6 times higher with clarithromycin. A 90% confidence interval of 0.01–0.02 for rifampicin means exposure fell by 98–99%.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for clinical pharmacology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free