Erythromycin-felodipine interaction: Magnitude, mechanism, and comparison with grapefruit juice*

Bailey, David G.; Bend, John R.; Arnold, J. Malcolm O.; Tran, Lan; Spence, J. David

doi:10.1016/s0009-9236(96)90163-0

Cited by 103 publications

(77 citation statements)

References 23 publications

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“…In addition, grapefruit juice does not appear to influence the clearance of CYP3A4 substrates when they are administered intravenously (5,8). Finally, the primary effect of grapefruit juice on orally administered medications is to increase peak serum concentration ( C max ) with little change in the subsequent rate of elimination as measured by half-life (26).…”

Section: Introductionmentioning

confidence: 99%

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Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

Lown¹,

Bailey²,

Fontana³

et al. 1997

J. Clin. Invest.

558

444

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The increase in oral availability of felodipine and other commonly used medications when taken with grapefruit juice has been assumed to be due to inhibition of CYP3A4, a cytochrome P450 that is present in liver and intestine. To evaluate the effect of repeated grapefruit juice ingestion on CYP3A4 expression, 10 healthy men were given 8 oz of grapefruit juice three times a day for 6 d. Before and after receiving grapefruit juice, small bowel and colon mucosal biopsies were obtained endoscopically, oral felodipine kinetics were determined, and liver CYP3A4 activity was measured with the [ 14 C N -methyl] erythromycin breath test in each subject.Grapefruit juice did not alter liver CYP3A4 activity, colon levels of CYP3A5, or small bowel concentrations of P-glycoprotein, villin, CYP1A1, and CYP2D6. In contrast, the concentration of CYP3A4 in small bowel epithelia (enterocytes) fell 62% ( P ϭ 0.0006) with no corresponding change in CYP3A4 mRNA levels. In addition, enterocyte concentrations of CYP3A4 measured before grapefruit juice consumption correlated with the increase in C max when felodipine was taken with either the 1st or the 16th glass of grapefruit juice relative to water ( r ϭ 0.67, P ϭ 0.043, and r ϭ 0.71, P ϭ 0.022, respectively). We conclude that a mechanism for the effect of grapefruit juice on oral felodipine kinetics is its selective downregulation of CYP3A4 in the small intestine. ( J. Clin. Invest. 1997. 99:2545-2553.)

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Section: Introductionmentioning

confidence: 99%

“…Felodipine was chosen because it is completely absorbed after oral administration with water (9) and its interaction with grapefruit juice has been well characterized (1,26).…”

Section: Introductionmentioning

confidence: 99%

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

Lown¹,

Bailey²,

Fontana³

et al. 1997

J. Clin. Invest.

558

444

View full text Add to dashboard Cite

show abstract

“…1 Moreover, they are all substrates for cytochrome P450 3A4. 6,7 Erythromycin was shown to increase felodipine levels by about 300% in 12 patients, 8 and several case reports have described significant cardiovascular toxicity in patients receiving a calcium-channel blocker in combination with erythromycin or clarithromycin. [9][10][11][12][13] In contrast, no reports describe such toxicity in patients given azithromycin, which is consistent with the observation that it does not inhibit cytochrome P450 3A4.…”

mentioning

confidence: 99%

The risk of hypotension following co-prescription of macrolide antibiotics and calcium-channel blockers

Wright¹,

Gomes²,

Mamdani³

et al. 2011

Canadian Medical Association Journal

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“…For example, case reports of DDI resulting in adverse effects have been published for terfenadine and ketoconazole (KTZ) (Honig et al, 1993), felodipine and erythromycin (Bailey et al, 1996), and cerivastatin and gemfibrozil (Staffa et al, 2002). Because most of these in vivo interactions have been interpreted as the result of metabolic inhibition by cytochrome P450 (P450) inhibitors, the prediction of clinically significant DDI in preclinical studies is clearly desirable and has been examined using several in vitro methodologies with hepatocytes and microsomal fractions obtained from human liver.…”

mentioning

confidence: 99%

Effect of Oral Ketoconazole on Intestinal First-Pass Effect of Midazolam and Fexofenadine in Cynomolgus Monkeys

Ogasawara¹,

Kume²,

Kazama³

2006

Drug Metab Dispos

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ABSTRACT:Because the expression of drug-metabolizing enzymes and drug efflux transporters has been shown in the intestine, the contribution of this tissue to the first-pass effect has become of significant interest. Consequently, a comprehensive understanding of the absorption barriers in key preclinical species would be useful for the precise characterization of drug candidates. In the present investigation, we evaluated the intestinal first-pass effect of midazolam (MDZ) and fexofenadine (FEX), typical substrates for CYP3A and P-glycoprotein (P-gp), respectively, with ketoconazole (KTZ) as a potent dual CYP3A/P-gp inhibitor in cynomolgus monkeys. When

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Erythromycin-felodipine interaction: Magnitude, mechanism, and comparison with grapefruit juice*

Cited by 103 publications

References 23 publications

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

The risk of hypotension following co-prescription of macrolide antibiotics and calcium-channel blockers

Effect of Oral Ketoconazole on Intestinal First-Pass Effect of Midazolam and Fexofenadine in Cynomolgus Monkeys

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