Atorvastatin grapefruit juice
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Effects of Grapefruit Juice on Atorvastatin Pharmacokinetics
Introduction to Atorvastatin and Grapefruit Juice Interaction
Atorvastatin, a widely used statin for lowering cholesterol, is known to interact with grapefruit juice (GFJ). This interaction primarily affects the drug's pharmacokinetics, leading to changes in its absorption and metabolism. Understanding these effects is crucial for optimizing atorvastatin therapy and minimizing potential adverse effects.
Increased Atorvastatin Bioavailability with Grapefruit Juice
Pharmacokinetic Changes
Multiple studies have demonstrated that grapefruit juice significantly increases the bioavailability of atorvastatin. In a randomized crossover study, GFJ increased the mean area under the curve (AUC) of atorvastatin acid by 83%1. Another study in Japanese subjects found a 1.40-fold increase in the AUC of atorvastatin acid when taken with GFJ2. These findings indicate that GFJ can substantially elevate atorvastatin levels in the bloodstream.
Clinical Implications
The clinical implications of this interaction were explored in a study where patients on stable atorvastatin doses consumed GFJ daily for 90 days. The results showed a 19% to 26% increase in serum atorvastatin levels without significant changes in lipid profiles or adverse effects on liver function and creatine phosphokinase (CPK)3. This suggests that while GFJ increases atorvastatin levels, it does not necessarily enhance its lipid-lowering efficacy or cause significant toxicity.
Mechanisms of Interaction
CYP3A4 Inhibition
The primary mechanism behind this interaction is the inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme by compounds in grapefruit juice. CYP3A4 is responsible for the presystemic metabolism of atorvastatin, and its inhibition leads to increased drug bioavailability1 2 7. This effect can persist for up to 24 hours after GFJ consumption7.
P-glycoprotein and OATP2B1 Inhibition
In addition to CYP3A4, GFJ also inhibits P-glycoprotein (P-gp) and organic anion transporting polypeptides (OATP2B1), which are involved in drug transport across cell membranes. This inhibition further enhances the bioavailability of atorvastatin by reducing its efflux from intestinal cells and increasing its absorption5 7.
Comparison with Other Statins
Differential Effects
The interaction between GFJ and atorvastatin is more pronounced compared to other statins. For instance, pitavastatin and pravastatin show minimal changes in pharmacokinetics when taken with GFJ1 2. This differential effect is attributed to the varying degrees of CYP3A4 metabolism among different statins.
Clinical Recommendations
Given the significant interaction with atorvastatin, it is generally recommended to avoid GFJ consumption during atorvastatin therapy. However, for statins like pravastatin and pitavastatin, which are less affected by GFJ, such dietary restrictions may not be necessary1 2.
Conclusion
Grapefruit juice significantly increases the bioavailability of atorvastatin by inhibiting CYP3A4 and other transport proteins. While this interaction does not appear to enhance the lipid-lowering effects of atorvastatin or cause significant toxicity, it underscores the importance of dietary considerations in statin therapy. Patients on atorvastatin should be advised to avoid grapefruit juice to maintain optimal drug efficacy and safety.
Sources and full results
Most relevant research papers on this topic
Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin.
Grapefruit juice increases the pharmacokinetics of atorvastatin, but not of pitavastatin, suggesting that pitavastatin is less affected by CYP3A4-mediated metabolism.
RCT
Highly CitedEffects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese.
Grapefruit juice significantly affects the pharmacokinetics of atorvastatin but has little or no effect on pravastatin in Japanese subjects.
RCTHighly CitedSerum concentrations and clinical effects of atorvastatin in patients taking grapefruit juice daily.
Daily grapefruit juice intake slightly increases atorvastatin levels without significantly affecting lipid profile or causing adverse liver or muscle effects.
Non-RCT
Rigorous JournalGrapefruit Juice and Statins.
Grapefruit juice consumption is not contraindicated while taking statins, as it increases their effectiveness in reducing cholesterol levels and heart disease risk.
Case ReportSmall-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP.
Grapefruit juice reduces drug exposure in small-dosing conditions, suggesting all 5 test drugs are substrates for OATP2B1, while atorvastatin does not affect exposure, and SLCO2B1*3 genotype has no effect.
Non-RCTEffects of Three Kinds of Juice of Mandarinorange on Pharmacokinetics of Atorvastatin in Healthy Volunteers
Three kinds of mandarin-orange juice showed no significantly influence on the pharmacokinetics of atorvastatin in healthy subjects.
RCTInteractions Between Grapefruit Juice and Cardiovascular Drugs
Grapefruit juice can alter oral drug pharmacokinetics, potentially increasing the risk of side effects and requiring alternative treatments for certain cardiovascular drugs.
Highly CitedEffects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin.
Regular consumption of grapefruit juice significantly increases the plasma concentrations of simvastatin and simvastatin acid, potentially increasing both the cholesterol-lowering effect and the risk of adverse effects.
RCTHighly CitedInteractions between drugs and grapefruit.
Grapefruit juice can interact with certain drugs, such as statins, requiring nurses to provide appropriate advice and report suspected interactions.
Toxicological and Pharmacokinetic Evaluation of Concomitant Intake of Grapefruit Juice and Simvastatin in Rats after Repeated Treatment over 28 Days.
Concomitant intake of simvastatin and grapefruit juice over 28 days in rats does not cause more pronounced toxic effects than simvastatin alone, with dose relationships potentially affecting the interaction.
Non-RCT
Animal Study