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Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid
Author(s) -
Kantola Teemu,
Kivistö Kari T.,
Neuvonen Pertti J.
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90034-0
Subject(s) - lovastatin , grapefruit juice , cmax , chemistry , citrus paradisi , pharmacokinetics , bioavailability , cyp3a4 , pharmacology , crossover study , food science , biochemistry , medicine , cholesterol , metabolism , biology , botany , cytochrome p450 , alternative medicine , pathology , rutaceae , placebo
Background Grapefruit juice increases the bioavailability of several drugs known to be metabolized by CYP3A4. We wanted to investigate a possible interaction of grapefruit juice with lovastatin, a cholesterollowering agent that is partially metabolized by CYP3A4. Methods An open, randomized, two‐phase crossover study with an interval of 2 weeks between the phases was carried out. Ten healthy volunteers took either 200 ml double‐strength grapefruit juice or water orally three times a day for 2 days. On day 3, each subject ingested 80 mg lovastatin with either 200 ml grapefruit juice or water, and an additional dose of 200 ml was ingested ½ and ½ hours after lovastatin intake. Serum concentrations of lovastatin and lovastatin acid were measured up to 12 hours. Results Grapefruit juice greatly increased the serum concentrations of both lovastatin and lovastatin acid. The mean peak serum concentration (C max ) of lovastatin was increased about 12‐fold (range, 5.2‐fold to 19.7‐fold; p < 0.001) and the area under the concentration‐time curve [AUC(0–12)] was increased 15‐fold (range, 5.7‐fold to 26.3‐fold; p < 0.001) by grapefruit juice. The mean C max and AUC(0–12) of lovastatin acid were increased about fourfold (range, 1.8‐fold to 11.5‐fold; p < 0.001) and fivefold (range, 2.4‐fold to 23.3‐fold; p < 0.001) by grapefruit juice, respectively. The half‐lives of lovastatin and lovastatin acid remained unchanged. Conclusions Grapefruit juice can greatly increase serum concentrations of lovastatin and its active metabolite, lovastatin acid, probably by preventing CYP3A4‐mediated first‐pass metabolism in the small intestine. The concomitant use of grapefruit juice with lovastatin and simvastatin should be avoided, or the dose of these 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors should be reduced accordingly. Clinical Pharmacology & Therapeutics (1998) 63 , 397–402; doi: