Zocor

[simvastatin]

Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma concentrations of drugs metabolized by CYP3A4. In one study 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 -hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/ tandem mass spectrometry] of 16-fold and 7-fold, respectively.

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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 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 its -hydroxyacid metabolite [measured using a chemical assay — liquid chromatography/ tandem mass spectrometry] of 1.88-fold and 1.31-fold, respectively. The effect of amounts of grapefruit juice between those used in these two studies on simvastatin pharmacokinetics has not been studied.

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