| Disease | TWO RANDOMIZED, TWO-PHASE CROSSOVER STUDIES WERE PERFORMED STUDY I WITH ATORVASTATIN IN 12 HEALTHY VOLUNTEERS AND STUDY II WITH PRAVASTATIN IN 11 HEALTHY VOLUNTEERS. IN BOTH STUDIES, VOLUNTEERS TOOK 200 ML DOUBLE-STRENGTH GRAPEFRUIT JUICE OR
WATER 3 TIMES A DAY FOR 2 DAYS. ON DAY 3, EACH SUBJECT INGESTED SINGLE 40 MG DOSE OF ATORVASTATIN (STUDY I) OR PRAVASTATIN (STUDY II) WITH EITHER 200 ML GRAPEFRUIT JUICE OR WATER, AND AN ADDITIONAL 200 ML WAS INGESTED 1/2 HOURS LATER. IN
ADDITION, SUBJECTS TOOK 200 ML GRAPEFRUIT JUICE OR WATER 3 TIMES A DAY ON DAYS 4 AND 5 IN STUDY I. IN STUDY I, SERUM CONCENTRATIONS OF ATORVASTATIN LACTONE, 2-HYDROXYATORVASTATIN ACID, 2-HYDROXYATORVASTATIN LACTONE, AND ACTIVE AND TOTAL 3-
HYDROXY-3-METHYLGLUTARYL COENZYME A (HMG-COA) REDUCTASE INHIBITORS WERE MEASURED UP TO 72 HOURS. IN STUDY II, PRAVASTATIN, PRAVASTATIN LACTONE, AND ACTIVE AND TOTAL HMG-COA REDUCTASE INHIBITORS WERE MEASURE UP TO 24 HOURS. GRAPEFRUIT JUICE
SIGNIFICANTLY INCREASED SERUM CONCENTRATIONS OF ATORVASTATIN ACID, ATORVASTATIN LACTONE, AND ACTIVE AND TOTAL HMG-COA REDUCTASE INHIBITORS, PROBALBLY BY DECREASING CYP3A4-MEDIATED FIRST-PASS METABOLISM OF ATORVASTTIN IN THE SMALL INTESTINE.
ON THE OTHER HAND, GRAPEFRUIT JUICE HAD NO EFECT ON THE PHARMACOKINETICS OF PRAVASTATIN. CONCOMITANT USE OF ATORVASTATIN AND AT LEAST LARGE AMOUNTS OF GRAPEFRUIT JUICE SHOULD BE AVOIDED, OR THE DOSE OF ATORVASTATIN SHOULD BE REDUCED ACCORDINGLY. |