Furanocoumarin from grapefruit (Citrus paradisi) peel oil and juice — the principal active component behind the grapefruit/CYP3A4 food-drug interaction. Mechanism-based (suicide) inactivator of intestinal CYP3A4: K_I = 7.7 µM, k_inact = 0.3 min⁻¹ on purified CYP3A4 (He 1998 PMID:9548795); K_I = 40 µM, k_inact 0.05-0.08 min⁻¹ in HLM (Tassaneeyakul 2000 PMID:10860553). Inactivation is irreversible — recovery requires de novo CYP3A4 synthesis (~24-72 h), which is why a single glass of grapefruit juice perturbs first-pass metabolism for the rest of the day. The clinically dominant effect is on enterocyte CYP3A4 (intestinal first-pass), not hepatic. Co-furanocoumarin 6′,7′-dihydroxybergamottin (DHB) is more potent in vitro (K_I 5.56 µM) and faster-onset.
Dosing Guidelines
PO: Typical 8 (Range: 6–12)
Target Organ Systems
digestive
Interactions
Felodipine (warn): The canonical grapefruit interaction. Goosen 2004 (PMID:15592332) verbatim: "With 12 mg bergamottin, felodipine C max increased by 40% (P < .05) and AUC increased by 37%". Mechanism: bergamottin is a mechanism-based CYP3A4 inactivator (K_I=7.7 µM, k_inact=0.3/min, He 1998 PMID:9548795 on purified CYP3A4). Schema models reversible Ki only; mechanism-based effect is described in compound mechanism prose, no structured kinetics block here.
Simvastatin (warn): Le Goff-Klein 2004 (PMID:15285845) verbatim: "in human liver microsomes the K(i) values are similar in BG and NRG (K(i)=34+/-5 microM and 29+/-11 microM, respectively)" measured against simvastatin metabolism. Reversible mixed-type Ki, distinct from the mechanism-based K_I (7.7 µM, He 1998) on CYP3A4 generally.