[Grapefruit juice and drugs: a hazardous combination?]. / Jus de pamplemousse et médicaments: une association à surveiller?

A single glass of grapefruit juice can improve the oral bioavailability of a drug thus either increasing its efficacy or enhancing its adverse effects particularly if the therapeutic index is narrow. Grapefruit juice acts by inhibiting presystemic drug metabolism mediated by CYP P450 3A4 in the small bowel and this interaction would appear to be more relevant if the CYP 3A4 content is high and the drug has a strong first pass degradation. Intestinal P-glycoprotein may also be affected by grapefruit juice. The compounds responsible for this food-drug interaction have not as yet been identified but this phenomenon could result from a complex synergy between flavonoids (naringin, naringenin), furanocoumarins (6',7'-dihydroxybergamottin, bergamottin) and sesquiterpen (nootkatone). In our study, we report the mechanisms of action of grapefruit juice and the interactions between grapefruit juice and 42 drugs; to date, only 12 drugs showed no interaction. Taking these results into consideration, patients should be educated about grapefruit juice intake with medication.

An experimental study of survival after two hours of normothermic hepatic ischemia.

Total hepatic inflow occlusion is well tolerated in pigs with normothermia for as long as two hours, provided that splanchnic venous pooling is avoided by active pumping through a splenojugular bypass. Hepatic dysfunction after 60, 90 and, even, 120 minutes of hepatic ischemia is mild and transient. Complete return to normal liver function tests is rapid. Early microscopic alterations of the liver are moderate, and no late abnormalities, such as cirrhosis or vascular changes, were observed one to three months later. Conversely, interruption of hepatic blood flow for three hours is not compatible with life. In this study, a previously unsuspected resistance of the pig liver to warm ischemia is demonstrated. These findings corroborate and extend those of recent clinical studies in which a similar tolerance of the human liver to prolonged normotherthermic ischemia is reported, thus questioning the necessity for deliberate hypothermia in operations involving the liver.