Effect of bile acids on the biliary excretion of pravastatin in rats

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Abstract

Aim:

The biliary excretion of pravastatin, an HMG-CoA reductase inhibitor, is mediated by the multidrug resistance protein 2, but a recent report suggests that pravastatin is also a substrate of the bile salt export pump, which transports bile acids. We examined the effects of bile acids on biliary pravastatin excretion in rats.

Methods:

The effect of taurocholate on biliary pravastatin excretion, and that of pravastatin on biliary taurocholate excretion was examined in bile-drained rats.

Results:

Taurocholate had no effect on biliary pravastatin excretion, whereas pravastatin with a dose to cause biliary excretory maximum significantly inhibited biliary taurocholate excretion.

Conclusion:

These data indicate that increased serum bile acids will not affect the pharmacokinetics of pravastatin in patients with hepatobiliary diseases. Although pravastatin inhibited biliary taurocholate excretion, it is unlikely that pravastatin significantly inhibits biliary bile acid excretion by its therapeutic doses.

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