| Disease | INVESTIGATION OF THE RENAL EXCRETION OF NARINGIN, NARINGENIN, AND ITS GLUCURONIDES AFTER ADMINISTRATION OF 20 ML GRAPEFRUIT JUICE (621 MICRO/L NARINGIN) PER KILOGRAM OF BODY WEIGHT TO SIX HEALTHY ADULTS. URINE WAS COLLECTED FOR 24 HOURS, AND
FLAVONOIDS WERE MEASURED BY HPLC IN ALIQUOTS WITH AND WITHOUT GLUCURONIDASE PRETREATMENT. NARINGIN OR NARINGIN GLUCURONIDES WERE NOT FOUND. NARINGENIN AND ITS GLUCURONIDES APPEARED IN URINE AFTER A MEDIAN LAG-TIME OF 2 HOURS AND REACHED 0.012%
TO 0.37% AND 5.0% TO 57%, RESPECTIVELY, OF THE MOLAR NARINGIN DOSE. IN ADDITIONAL INVESTIGATIONS, LOW CONCENTRATIONS (<4 MICRO/L) OF NARINGENIN GLUCURONIDES, BUT NEITHER NARRINGIN NOR NARINGENIN WERE FOUND IN PLAMA SAMPLES FROM PREVIOUS GRAPE-
FRUIT JUICE INTERACTION STUDIES, AND METABOLIZATION OF NARINGIN TO NARINGENIN OCCURRED DURING 24 HOURS OF INCUBATION (37C) IN THREE OF FIVE FECES SAMPLES TESTED. THE DATA SUGGEST THAT CLEAVAGE OF THE SUGAR MOIETY, PRESUMABLY BY INTESTINAL
BACTERIA, IS THE FIRST STEP OF NARINGIN METABOLISM. NARINGENIN FORMATION IS THOUGHT TO BE THE CRUCIAL STEP IN DETERMINATION OF BIOAVAILABILY OF THE COMPOUND, WHICH UNDERGOES RAPID GLUCURONIDATION. |