Orange juice substantially reduces the bioavailability of the β‐adrenergic–blocking agent celiprolol

Lilja, Jari J.; Juntti‐Patinen, Laura; Neuvonen, Pertti J.

doi:10.1016/j.clpt.2003.11.002

Cited by 93 publications

(69 citation statements)

References 13 publications

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“…In contrast to FJ-drug interactions involving CYP3A substrates, decreased bioavailability of OATP2B1 substrates was observed with not only GFJ, but also OJ and AJ (Dresser et al, 2002;Lilja et al, 2004Lilja et al, , 2005Imanaga et al, 2011;Tapaninen et al, 2011;Jeon et al, 2013). Naringin, the main constituent flavonoid of GFJ, is thought to be a major inhibitor of OATP2B1-mediated drug transport in GFJ Shirasaka et al, 2009Shirasaka et al, , 2010aShirasaka et al, , b, 2011aShirasaka et al, , b, 2013 that in GFJ, it is unlikely that naringin is a major contributor to OATP2B1-mediated drug interactions involving OJ and AJ (Ameer et al, 1996;Ho et al, 2000).…”

Section: Introductionmentioning

confidence: 85%

Long-Lasting Inhibitory Effect of Apple and Orange Juices, but Not Grapefruit Juice, on OATP2B1-Mediated Drug Absorption

et al. 2012

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Enzyme-based grapefruit juice (GFJ)-drug interactions are mainly due to mechanism-based irreversible inhibition of metabolizing enzyme CYP3A4 by GFJ components, but the transporter organic anion transporting polypeptide (OATP)2B1 is also a putative site of interaction between drugs and fruit juices (FJ) in the absorption process. Here we aimed to investigate the effect of preincubation with FJ on OATP2B1-mediated transport of drugs in vitro. When OATP2B1-expressing Xenopus oocytes were preincubated with GFJ, orange juice (OJ), or apple juice (AJ), AJ induced a remarkable decrease in OATP2B1-mediated estrone-3-sulfate uptake in a concentration-dependent manner (IC 50 = 1.5%). A similar but less potent effect was observed with OJ (IC 50 = 21%), whereas GFJ had no effect. Similar results were obtained in preincubation studies using fexofenadine. Preincubation with OJ and AJ resulted in timedependent inhibition of OATP2B1. Again, AJ had the more potent effect; its action lasted for at least 240 minutes, suggesting that AJ irreversibly inhibits OATP2B1-mediated drug uptake. Kinetic analysis revealed that coincubation and preincubation with AJ reduced OATP2B1-mediated estrone-3-sulfate uptake via competitive and noncompetitive mechanisms, respectively. Thus, OATP2B1 is functionally impaired through both competitive and long-lasting inhibition mechanisms by AJ and OJ, but not GFJ. Interestingly, although GFJ but not AJ is able to irreversibly inhibit CYP3A4, in the case of OATP2B1, AJ but not GFJ has a long-lasting inhibitory effect. Accordingly, complex FJ-drug interactions may occur in vivo, and their clinical significance should be examined.

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Section: Introductionmentioning

confidence: 85%

Long-Lasting Inhibitory Effect of Apple and Orange Juices, but Not Grapefruit Juice, on OATP2B1-Mediated Drug Absorption

et al. 2012

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“…Despite the lack of an effect of cranberry juice on the pharmacokinetics of warfarin (20), several case reports have indicated that cranberry juice results in an enhanced antithrombotic effect of warfarin (8,12,23,27,32,33), suggesting a possible pharmacodynamic effect. A number of studies have reported incidences of apple-, orange-, and grapefruit-drug interactions (6,7,21,29). The potential effect of cranberry juice on drug transporters had not been investigated prior to our study.…”

Section: Discussionmentioning

confidence: 99%

“…It is now known that fruit juices are capable of producing clinically significant drug interactions through the inhibition of carriermediated active transport (6). For example, the levels of absorption of fexofenadine (7), talinolol (29), and celiprolol (21) were markedly reduced by the concurrent ingestion of grapefruit, orange, and apple juices. Although the molecular mechanisms of intestinal transport remain largely unknown, the furanocoumarins and bioflavonoids present in these juices were shown to be potent in vitro inhibitors of organic aniontransporting polypeptides and are suggested to play a role in the observed juice interactions (7).…”

mentioning

confidence: 99%

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Li¹,

Andrew

Wang³

et al. 2009

Antimicrob Agents Chemother

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Cranberry juice consumption is often recommended along with low-dose oral antibiotics for prophylaxis for recurrent urinary tract infection (UTI). Because multiple membrane transporters are involved in the intestinal absorption and renal excretion of ␤-lactam antibiotics, we evaluated the potential risk of pharmacokinetic interactions between cranberry juice and the ␤-lactams amoxicillin (amoxicilline) and cefaclor. The amoxicillin-cranberry juice interaction was investigated in 18 healthy women who received on four separate occasions a single oral test dose of amoxicillin at 500 mg and 2 g with or without cranberry juice cocktail (8 oz) according to a crossover design. A parallel cefaclor-cranberry juice interaction study was also conducted in which 500 mg cefaclor was administered with or without cranberry juice cocktail (12 oz). Data were analyzed by noncompartmental methods and nonlinear mixed-effects compartmental modeling. We conclude that the concurrent use of cranberry juice has no significant effect on the extent of oral absorption or the renal clearance of amoxicillin and cefaclor. However, delays in the absorption of amoxicillin and cefaclor were observed. These results suggest that the use of cranberry juice at usual quantities as prophylaxis for UTI is not likely to alter the pharmacokinetics of these two oral antibiotics.

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“…Orange juice contains minor amounts of furanocoumarins and has little CYP3A4 inhibitory effect Won et al, 2010). It has been demonstrated that orange juice reduces the AUC of celiprolol (Lilja et al, 2004), atenolol (Lilja et al, 2005), fexofenadine (Dresser et al, 2002), ciprofloxacin (Neuhofel et al, 2002), and levofloxacin (Wallace et al, 2003). Because at least some of these drugs (e.g., fexofenadine, celiprolol) have been identified as substrates of OATPs expressed in the intestine, uptake inhibition of these transporters may be the cause for these interactions.…”

Section: Drug-food Interactionsmentioning

confidence: 99%

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

2013

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Orange juice substantially reduces the bioavailability of the β‐adrenergic–blocking agent celiprolol

Cited by 93 publications

References 13 publications

Long-Lasting Inhibitory Effect of Apple and Orange Juices, but Not Grapefruit Juice, on OATP2B1-Mediated Drug Absorption

Long-Lasting Inhibitory Effect of Apple and Orange Juices, but Not Grapefruit Juice, on OATP2B1-Mediated Drug Absorption

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects

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