Pravastatin and grapefruit interaction
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Grapefruit Juice and Pravastatin Interaction: Mechanisms and Clinical Impact
Grapefruit Juice, OATP Transporters, and Pravastatin Absorption
Grapefruit juice (GFJ) is known to interact with various medications, often by affecting drug transporters such as organic anion transporting polypeptides (OATPs). Studies show that GFJ can inhibit OATP-mediated drug uptake, but the effect is highly substrate-dependent. For pravastatin, GFJ strongly inhibits its uptake at the high-affinity site of the OATP2B1 transporter, but not at the low-affinity site. Importantly, at therapeutic concentrations, pravastatin is mainly transported via the low-affinity site, which is not significantly affected by GFJ. This explains why, in clinical settings, GFJ does not meaningfully reduce pravastatin bioavailability in humans, even though in vitro studies show some inhibition at certain binding sites .
Animal Studies: Pravastatin Absorption and Naringin
In animal models, particularly in rats, GFJ and its main flavonoid component naringin have been shown to decrease the absorption of pravastatin. This is due to the inhibition of Oatp-mediated transport in the intestine. However, these findings in rats do not fully translate to humans, where the clinical impact appears minimal 24.
Clinical Studies: Grapefruit Juice and Pravastatin Pharmacokinetics
Human studies confirm that GFJ has little or no significant effect on the pharmacokinetics of pravastatin. When healthy volunteers consumed GFJ with pravastatin, there were no significant changes in the drug’s plasma concentration or overall exposure, except for a minor increase in pravastatin lactone, a metabolite with unclear clinical relevance. This contrasts with other statins like atorvastatin, where GFJ significantly increases drug levels .
Comparison with Other Statins and Mechanistic Insights
The interaction between GFJ and statins is mainly due to the inhibition of CYP3A4, P-glycoprotein (P-gp), and OATPs. However, pravastatin is less affected because it is not extensively metabolized by CYP3A4 and relies on OATP transporters that are less susceptible to GFJ inhibition at therapeutic doses. This is in contrast to other statins, such as simvastatin and atorvastatin, which show significant increases in plasma levels when taken with GFJ, leading to a higher risk of side effects .
Conclusion
Overall, while grapefruit juice can inhibit certain drug transporters and affect the absorption of some statins, its impact on pravastatin is minimal at clinically relevant doses. Patients taking pravastatin generally do not need to avoid grapefruit juice, as the risk of a significant drug interaction is low 135.
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