Effects of grapefruit juice ingestion - pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men

Abstract

The main acute effect of the grapefruit juice on the plasma concentrations of felodipine is mediated by inhibition of gut wall metabolism.

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

“…Grapefruit juice caused a significant increase in the bioavailability of drugs exhibiting the interaction, after oral dosing. However, after intravenous administration of the same drugsFgrapefruit juice altered neither pharmacokinetic nor pharmacodynamic parameters (Ducharme et al, 1995;Lundahl et al, 1997;Uno et al, 2000). Hence, it has been concluded that only intestinal CYP3A4 is inhibited by grapefruit juice, while liver resident CYP3A4 enzymes are not affected.…”

“…It should be noted that an especially pronounced pharmacokinetic effect has been detected among elderly subjects . Most of these studies reported further decreases in diastolic blood pressure when felodipine was taken with grapefruit juice, as well as increase in haemodynamic-related adverse effects such as increased heart rate and orthostatic hypotension (Bailey et al, 1991;Lundahl et al, 1997Lundahl et al, , 1998. Other dihydropyridines exhibiting the interaction to a similar extent are nisoldipine (Bailey et al, 1993b;Takanaga et al, 2000) and nicardipine .…”

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?

“…The pharmacokinetics of intravenously administered drugs are unchanged. 9,10 Because these chemicals are innate to grapefruit, all forms of the fruit (freshly squeezed juice, frozen concentrate and whole fruit) have the po tential to reduce the activity of CYP3A4. One whole grapefruit or 200 mL of grapefruit juice is sufficient to cause clinically relevant increased systemic drug concentration and subsequent adverse effects.…”

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study

“…Subsequent investigations found that through the inhibition of the CYP3A4 enzyme system, primarily in the liver and small intestine (Guengerich, 1999;Veronese et al, 2003), grapefruit juice interacts with more than 60% of orally administered drugs leading to elevation of their serum concentrations (Maskalyk, 2002;Bailey and Dresser, 2004). Consumption of a single glass (six ounces) can produce the maximal acute pharmacokinetic effect (Edgar et al, 1992;Lundahl et al, 1995Lundahl et al, , 1997Dahan and Altman, 2004) with enhanced oral drug bioavailability occurring up to 24 h after juice consumption (Bailey and Dresser, 2004).Since 1989, the list of drug interactions with grapefruit juice has expanded to include oral 17b-oestradiol and progesterone (Guengerich, 1999;Maskalyk, 2002; Medical Letter, 2005). The US Food and Drug Administration (FDA) mandated labelling for hormone products for postmenopausal women now contains warnings that grapefruit juice may increase plasma concentrations of oestrogen (US Food and Drug Administration, 2006).…”