Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese

Article date: April 2004

By: Ichiro Fukazawa, Naoki Uchida, Eiji Uchida, Hajime Yasuhara, in Volume 57, Issue 4, pages 448-455

Aims

To investigate the effects of repeated grapefruit juice (GFJ) intake on the pharmacokinetics of atorvastatin and pravastatin in Japanese subjects.

Methods

Two randomized, two‐way crossover studies were performed. GFJ or water was given to two groups of 10 subjects each three times daily for 2 days. On the third day, single 10 mg doses of atorvastatin or pravastatin were orally administered with GFJ or water, and an additional 250 ml of GFJ or water was taken before lunch and dinner. Plasma concentrations of atorvastatin and its metabolites were determined over 48 h postdosing and of pravastatin and its metabolites over 24 h postdosing.

Results

Compared with in the water group, the AUC(0,48 h) of atorvastatin acid significantly increased by 1.40 fold (95% CI 1.02, 1.92; P < 0.05) when atorvastatin was taken with GFJ. AUC(0,48 h) and Cmax of atorvastatin lactone significantly increased by 1.56 (95% CI 1.33, 1.83; P < 0.001) and 1.29 fold (95% CI 1.09, 1.51; P < 0.01), respectively, when atorvastatin was taken with GFJ. No significant changes were detected in any pravastatin pharmacokinetic parameter examined when pravastatin was taken with GFJ. However, AUC(0,24 h) of pravastatin lactone increased 1.31 fold (95% CI 1.01, 1.71; P < 0.05) with GFJ intake.

Conclusions

GFJ was confirmed to significantly affect the pharmacokinetics of atorvastatin but had little or no effect on those of pravastatin in Japanese subjects.

DOI: 10.1046/j.1365-2125.2003.02030.x

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