Summary
Bergamottin and 6',7'-dihydroxybergamottin in grapefruit irreversibly inactivate intestinal CYP3A4 via mechanism-based covalent binding, reducing enzyme abundance by 50-70% after a single 200 ml serving. Full resynthesis takes 24-72 hours, meaning timing separation of grapefruit and medication does not prevent interactions. Parallel inhibition of intestinal P-glycoprotein raises systemic exposure to many substrates, while OATP1A2 blockade can paradoxically lower absorption of drugs like fexofenadine. Interaction magnitude varies with cultivar (white > ruby red), processing method, and individual CYP3A4 expression. Seville orange, tangelo and pomelo contain identical furanocoumarins and pose similar risks.
Dose Information
| ROA | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| Oral | 100-200ml | - | - | - |
Light
Common
Strong
Heavy
Onset, Duration & After-effects
| ROA | Onset | Comeup | Peak | Offset | After Effects |
|---|---|---|---|---|---|
| Oral | 15-30 min | 30-60 min | 30 min | 24 hrs | 24-72 hrs |
Tolerance
Build-up
varies by mechanism; therapeutic tolerance may develop over weeks of regular use
Reset
typically days to weeks after discontinuation
Effects
Positive
- Mild digestive stimulation
Negative
Neutral
- Bitter-sweet citrus flavor