Effects of Grapefruit Juice Consumption on Pharmacokinetics of Low Dose Simvastatin: Cross-over Study with a Review of the Literature
2012
The effects of consumption of grapefruit juice on the pharmacokinetics of conventional low-dose simvastatin in Japan were investigated. In a randomized cross-over study with two phases, 10 healthy volunteers ingested grapefruit juice 400ml or water for 2 days. On day 3, a single 5mg dose of simvastatin was administered with grapefruit juice 200ml or water. Plasma concentrations of HMG-CoA reductase inhibitor were determined up to 8 h thereafter. Grapefruit juice increased the area under the plasma concentration-time curves from 0 to 8 h of total HMG-CoA reductase inhibitor 1.7- fold (p=0.002) and that of active HMG-CoA reductase inhibitor 1.7-fold (p=0.024). However, the peak concentrations (Cmax) and Tmax of total and active HMG-CoA reductase inhibitors were not significant influenced.Consumption of grapefruit juice with low-dose simvastatin thus resulted in mild increase of the plasma HMG-CoA reductase inhibitor, so that the pharmacokinetic interaction can be labeled as of weak CYP3A type.
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