Experiment 626233
Worktypes
Compounds isolated
Details
| Property | Value |
|---|---|
| Pharmacology | |
| Administration route | ORAL |
| Organism | Citrus paradisi (RUTACEAE) |
| Citation | BAILEY,DG: KREEFT,JH: MUNOZ,C: FREEMAN,DJ: BEND,JAR:. (1998). GRAPEFRUIT JUICE-FELODIPINE INTERACTION: EFFECT OF NARINGIN AND 6',7'-DIHYDROXYBERGAMOTTIN IN HUMANS.. 64(3) |
| Amount utilized | |
| Compound isolated | |
| Disease | THE EFFECT OF FRACTIONS, GRAPEFRUIT JUICE (CONTAINING COMPARABLE AMOUNTS OF BOTH FRACTIONS), AND WATER ON THE PHARMACOKINETICS OF ORAL FELODIPINE WERE ASSESSED IN 12 HEALTHY MEN IN A RANDOMIZED, 4-WAY CROSSOVER STUDY. THE AMOUNTS OF NARINGIN AND 6'-7'-DIHYDROXYBERGAMOTIN IN THE SUPERNATANT FRACTION (148 MG AND 1.85 MG) WERE GREATER THAN IN THE PARTICULATE FRACTION (7 MG AND 0.60 MG). THE AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE (AUC) AND THE PEAK CONCENTRATION (CMAX) OF FELODIPINE WERE HIGHER WITH SUPERNATANT FRACTION (81 NMOL H/L AND 20 NMOL/L), PARTICULATE FRACTION (117 NMOL H/L AND 24 NMOL/L), AND GRAPEFRUIT JUICE (130 NMOL H/L AND 33 NMOL/L) COMPARED WITH WATER (53 NMOL H/L AND 11 NMOL/L). HOWEVER, THE SUPERNATANT FRACTION HAD A LOWER AUC FOR FELODIPINE AND A SIMILAR CMAX OF FELODIPINE RELATIVE TO THE PARTICULATE FRACTIOHN. THE SUPERNATANT FRACTION NEITHER AUGMENTED THE AUC OF THE PRIMARY METABOLITE DEHYDROFELODIPINE NOR DECREASED THE AUC RATIO OF DEHYDROFELODIPINE TO FELODIPINE COMPARED WITH WATER. INDIVIDUALLY THE SUPERNATANT FRACTION CONSISTENTLY PRODUCED LOWER FELODIPINE AUC AND CMAX COMPARED WITH GRAPEFRUIT JUICE. IN CONTRAST, THE PARTICULATE FRACTION HAD VALUES RANGING FROM MORE THAN GRAPEFRUIT JUICE TO LESS THAN SUPERNATANT FRACTION. NARINGIN AND 6',7'-DIHYDROXYBERGAMOTTIN ARE NOT THE MAJOR ACTIVE INGREDIENTS, ALTHOUGH THEY MAY CONTRIBUTE TO THE GRAPEFRUIT JUICE-FELODIPINE INTERACTION. THE VARIABLE EFFECT WITH THE PARTICULATE FRACTION MAY RESULT FROM ERRATIC BIOAVAILABILITY OF UNIDENTIFIED PRIMARY ACTIVE SUBSTANCES. THE FINDINGS SHOW THE IMPORTANCE OF IN VIVO TESTING TO DETERMINED THE INGREDIENTS IN GRAPEFRUIT JUICE RESPONSIBLE FORM INHIBITION OF CYTOCHROME P450 3A4 IN HUMANS. |
| Dose amount | VAR |
| Number | 3 |
| Qualitative result | . |
| Animal | HUMAN ADULT |
| Dose expression | DOSE |
| Gender | MALE |