Experiment 642181
Worktypes
Details
| Property | Value |
|---|---|
| Pharmacology | |
| Administration route | ORAL |
| Organism | Citrus paradisi (RUTACEAE) |
| Citation | VAN AGTMAEL,MA: GUPTA,V: VAN DER GRAAF,CAA: VAN BOXTEL,CJ:. (1999). THE EFFECT OF GRAPEFRUIT JUICE ON THE TIME-DEPENDENT DECLINE OF ARTEMETHER PLASMA LEVELS IN HEALTHY SUBJECTS.. 66(4) |
| Amount utilized | |
| Compound isolated | |
| Disease | IN A RANDOMIZED, TWO-PHASE CROSSOVER STUDY, 8 HEALTHY MALE SUBJECTS TOOK 100 MG ORAL ARTEMETHER WITH 350 ML WATER OR WITH 350 ML DOUBLE-STRENGTH FRESH FROZEN GRAPEFRUIT JUICE ONCE DAILY FOR 5 DAYS. ON DAY 1 AND DAY 5, 17 BLOOD SAMPLES WERE COLLECTED OVER A PERIOD OF 8 HOURS. THE MEAN PEAK ARTEMETHER PLASMA CONCENTRATION (CMAX) AND THE MEAN AREA UNDER CONCENTRATION TIME CURVE (AUC) AFTER THE LAST DOSE AT DAY 5 WERE ABOUT ONE THIRD COMPARED WITH DAY 1, WITHOUT A CHANGE IN THE ELIMINATION HALF-LIFE AFTER INTAKE WITH WATER (P=.006 FOR CMAX, P=.005 FOR AUC) AND WITH GRAPEFRUIT JUICE (P<.001 FOR CMAX AND AUC). GRAPEFRUIT JUICE INCREASED CMAX(P=.021) ANDAUC (P<.001)TWOFOLD ON DAY 1 (P=.021 AND DAY 5 (P=.05 FOR C MAX; P=.004 FOR AUC). DIHYDROARTEMISININ, THE ACTIVE METABOLITE, SHOWED A TWOFOLD INREASE IN CMAX (P=.006) AND AUC(P=.001) WITH GRAPEFRUIT JUICE, WITHOUT TOME-DEPENDENT CHANGES OF PHARMACOKINETIC PARAMETERS. GRAPEFRUIT JUICE SIGNIFICANTLY INCREASED THE ORAL BIOAVAILABILITY OF ARTEMETHER BUT DID NOT PREVENT THE TIME-DEPENDENT REDUCTION IN BIOAVAILABILITY. IT SUGGESTS THAT CYP3A4 IN THE GUT WALL IS ONE OF THE METABOLIZING ENZYMES OF ARTEMETHER BUT SEEMS TO NOT BE INVOLVED IN THE AUTOINDUCTION PROCESS. |
| Dose amount | 350.0 ML |
| Number | 1 |
| Qualitative result | . |
| Animal | HUMAN ADULT |
| Per unit | DAY |
| Dose expression | DOSE |
| Extract | FRUIT JUICE |
| Gender | MALE |