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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects.

Aim To examine the effect of grapefruit juice, an inhibitor of CYP3A4 in the small intestine, on the disposition of manidipine enantiomers in healthy subjects. Methods A randomized cross-over study with at least a 2-week wash-out period was performed. Seven healthy male volunteers received an oral 40-mg dose of racemic manidipine after an overnight fast with either grapefruit juice (GFJ) or water, as a control study. Plasma concentrations of (S)- and (R)-manidipine were monitored up to 10 h after the dosing. Results The plasma concentrations of (S)-manidipine were significantly higher (P < 0.001) than those of (R)-manidipine in the control phase with an S/R ratio for the AUC(0-infinity) of 1.62 (95% confidence interval 1.52, 1.73). GFJ significantly increased C(max) and AUC(0-infinity) of (S)-manidipine by 2.4-fold (P < 0.01) and 2.3-fold (P < 0.01), respectively, and C(max) and AUC(0-infinity) of (R)-manidipine were increased by 3.4-fold (P < 0.01) and 3.0-fold (P < 0.01), respectively. There were significant differences (P < 0.01) in GFJ-mediated percentage increases in C(max) and AUC(0-infinity) of (S)-manidipine compared with those of (R)-manidipine. The S/R ratio for AUC(0-infinity) was significantly decreased from 1.6 to 1.2 during the GFJ phase (P < 0.01). Conclusion These results indicate that the stereoselective disposition of manidipine was altered by GFJ, as an inhibitor of CYP3A4. GFJ appears to affect this metabolic disposal of (R)-manidipine to a greater extent than that of (S)-manidipine.[1]


  1. Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects. Uno, T., Ohkubo, T., Motomura, S., Sugawara, K. British journal of clinical pharmacology. (2006) [Pubmed]
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