Article date: September 2011
By: Patrick Reddy, David Ellington, Yiliang Zhu, Immo Zdrojewski, Sarah J. Parent, Jerold S. Harmatz, Hartmut Derendorf, David J. Greenblatt, Kevin Browne, Jr, in Volume 72, Issue 3, pages 434-441
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• In previous studies of healthy volunteers, administration of atorvastatin with very large quantities of grapefruit juice increases exposure to atorvastatin by a mean factor of 3.3. However more typical quantities of grapefruit juice increased exposure only by a factor of 1.3. The effects of customary doses of grapefruit juice on the efficacy and safety of atorvastatin in patients requiring treatment with this drug have not been established.
WHAT THIS STUDY ADDS
• The present study is the first to evaluate changes in the lipid‐lowering efficacy of atorvastatin, as well as subjective and laboratory assessments of safety, in a series of hyperlipidaemic patients on stable doses of atorvastatin who co‐ingested typical quantities of grapefruit juice. The findings indicate a small elevation of serum atorvastatin concentrations due to grapefruit juice, but no meaningful enhancement of lipid‐lowering effects, and no evidence of adverse liver or muscle effects.
AIM To determine whether customary exposure to grapefruit juice (GFJ) alters serum concentrations, effectiveness, and potential adverse effects of atorvastatin in patients requiring the medication.
METHODS Patients receiving extended treatment with atorvastatin (10, 20 or 40 mg day−1) at a stable dose received 300 ml day−1 of 100% GFJ for a period of 90 days. One cohort of patients (arm A, n= 60) continued on their current dose of atorvastatin; the second cohort (arm B, n= 70) reduced the daily dose by 50%. Serum atorvastatin, lipid profile, liver functions, and creatine phosphokinase (CPK) were measured at baseline and at 30, 60, and 90 days after starting GFJ.
RESULTS In Arm A patients, co‐ingestion of GFJ significantly elevated serum atorvastatin by 19% to 26% compared with baseline. Changes in lipid profile relative to baseline were negligible. There were no adverse effects on liver function tests or CPK. In arm B patients, serum atorvastatin declined by 12% to 25% compared to baseline, with a small but significant unfavourable effect in serum lipid profile. There were no adverse effects on liver function tests or CPK.
CONCLUSION In patients on extended stable atorvastatin treatment, addition of daily GFJ in typical quantities slightly elevates serum atorvastatin concentrations, but has no meaningful effect on the serum lipid profile, and causes no detectable adverse liver or muscle effects. Reduction of atorvastatin dosage when moderate amounts of GFJ are co‐ingested does not appear to be necessary.
DOI: 10.1111/j.1365-2125.2011.03996.x
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