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In one study<>footnote-2 2], 10 subjects consumed 200 mL of double-strength grapefruit juice (one can of frozen concentrate diluted with one rather than 3 cans of water) three times daily for 2 days and an additional 200 mL double-strength grapefruit juice together with, and 30 and 90 minutes following, a single dose of 60 mg simvastatin on the third day. This regimen of grapefruit juice resulted in mean increases in the concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity <measured>using a radioenzyme inhibition assay both before (for active inhibitors) and after (for total inhibitors) base hydrolysis] of 2.4-fold and 3.6-fold, respectively, and of simvastatin and its β-hydroxyacid metabolite <measured>using a chemical assay — liquid chromatography/tandem mass spectrometry] of 16-fold and 7-fold, respectively. In a second study, 16 subjects consumed one 8 oz glass of single-strength grapefruit juice (one can of frozen concentrate diluted with 3 cans of water) with breakfast for 3 consecutive days and a single dose of 20 mg simvastatin in the evening of the third day. This regimen of grapefruit juice resulted in a mean increase in the plasma concentration (as measured by the area under the concentration-time curve) of active and total HMG-CoA reductase inhibitory activity <using>a validated enzyme inhibition assay different from that used in the first<>footnote-2 2] study, both before (for active inhibitors) and after (for total inhibitors) base hydrolysis]of 1.13-fold and 1.18-fold, respectively, and of simvastatin and itsβ-hydroxyacid metabolite <measured>using a chemical assay — liquid chromatography/tandem mass spectrometry] of 1.88-fold and 1.31-fold, respectively. 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