Document Detail

Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin.
MedLine Citation:
PMID:  15206993     Owner:  NLM     Status:  MEDLINE    
AIMS: Simvastatin, a substrate for CYP3A4, is extensively metabolized during the first pass. Our aim was to investigate the effect of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin.
METHODS: In a randomized cross-over study with two phases, 10 healthy volunteers ingested grapefruit juice 200 ml or water (control) for 3 days. On day 3, a single 40-mg dose of simvastatin was administered with grapefruit juice 200 ml or water. Plasma concentrations of simvastatin and simvastatin acid were determined up to 24 h.
RESULTS: Grapefruit juice increased the area under the plasma concentration-time curves from 0 to 24 h [AUC(0-24)] of simvastatin 3.6-fold (range 1.8-6.0-fold; P < 0.01) and that of simvastatin acid 3.3-fold (range 2.1-5.6-fold; P < 0.01), respectively. The peak concentrations (C(max)) of simvastatin and simvastatin acid were increased 3.9-fold (range 2.3-9.3-fold; P < 0.01) and 4.3-fold (range 2.7-7.9-fold; P < 0.01) by grapefruit juice.
CONCLUSIONS: Even one glass of grapefruit juice, taken daily, considerably increases the plasma concentrations of simvastatin and simvastatin acid. Grapefruit juice may increase both the cholesterol-lowering effect and the risk of adverse effects of simvastatin.
Jari J Lilja; Mikko Neuvonen; Pertti J Neuvonen
Related Documents :
3072663 - The relationship between acid reduction and rate of ulcer healing.
847393 - Acetylsalicyclic acid and gastrointestinal propulsion in the rat.
6447383 - Interaction of plasmin with tranexamic acid and alpha 2 plasmin inhibitor in the plasma...
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  58     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-21     Completed Date:  2004-10-12     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  56-60     Citation Subset:  IM    
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anticholesteremic Agents / pharmacokinetics*
Cross-Over Studies
Food-Drug Interactions
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
Simvastatin / analogs & derivatives*,  metabolism,  pharmacokinetics*
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 79902-63-9/Simvastatin; 9L6M5TH46B/simvastatin acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Effects of tetracycline on the pharmacokinetics of halofantrine in healthy volunteers.
Next Document:  Determining the reporting quality of RCTs in clinical pharmacology.