Medicinal Chemistry

Effects of Grapefruit Juice Consumption on Pharmacokinetics of Low Dose Simvastatin: Cross-over Study with a Review of the Literature

Abstract

Akira Kurata, Hiroyuki Hagiwara, Taketomo Ohmomo, Sachio Suzuki, Kuniaki Nakahara, Shingo Konno, Chihiro Kijima, Madoka Inukai, Hitoshi Ozawa, Kiyotaka Fujii and Masataka Majima

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.