Inhibitory Effects of Citrus Fruits on Cytochrome P450 3A (CYP3A) Activity in Humans

Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin <i>N</i>-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.

Download Full-text

The Effects of Modifying In Vivo Cytochrome P450 3A (CYP3A) Activity on Etoricoxib Pharmacokinetics and of Etoricoxib Administration on CYP3A Activity

The Journal of Clinical Pharmacology ◽

10.1177/0091270004268129 ◽

2004 ◽

Vol 44 (10) ◽

pp. 1125-1131 ◽

Cited By ~ 11

Author(s):

Nancy G. B. Agrawal ◽

Catherine Z. Matthews ◽

Ralph S. Mazenko ◽

Eric J. Woolf ◽

Arturo G. Porras ◽

...

Keyword(s):

Cytochrome P450 ◽

Cyp3a Activity ◽

Cytochrome P450 3A

Download Full-text

Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients

Scientific Reports ◽

10.1038/s41598-019-51279-6 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Marcus J. P. Geist ◽

Victoria C. Ziesenitz ◽

Hubert J. Bardenheuer ◽

Juergen Burhenne ◽

Gisela Skopp ◽

...

Keyword(s):

Cytochrome P450 ◽

Cancer Patients ◽

Plasma Concentrations ◽

Real Life ◽

Metabolic Clearance ◽

Cyp3a Activity ◽

Cytochrome P450 3A ◽

Transdermal Fentanyl ◽

Large Variability ◽

Control Pain

Abstract Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1′-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination.

Download Full-text

POTENT INHIBITION BY STAR FRUIT OF HUMAN CYTOCHROME P450 3A (CYP3A) ACTIVITY

Drug Metabolism and Disposition ◽

10.1124/dmd.32.6.581 ◽

2004 ◽

Vol 32 (6) ◽

pp. 581-583 ◽

Cited By ~ 42

Author(s):

Muneaki Hidaka ◽

Ken-ichi Fujita ◽

Tetsuya Ogikubo ◽

Keishi Yamasaki ◽

Tomomi Iwakiri ◽

...

Keyword(s):

Cytochrome P450 ◽

Cyp3a Activity ◽

Cytochrome P450 3A ◽

Star Fruit ◽

Human Cytochrome ◽

Potent Inhibition

Download Full-text

In vitro and in vivo Inhibitory Effects of Glycyrrhetinic Acid on Cytochrome P450 3A Activity

Pharmacology ◽

10.1159/000320956 ◽

2010 ◽

Vol 86 (5-6) ◽

pp. 287-292 ◽

Cited By ~ 16

Author(s):

Hai Yun Li ◽

Wen Xu ◽

Juan Su ◽

Xi Zhang ◽

Li Wei Hu ◽

...

Keyword(s):

Cytochrome P450 ◽

Glycyrrhetinic Acid ◽

Cytochrome P450 3A ◽

Inhibitory Effects

Download Full-text

Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.2005.02343.x ◽

2005 ◽

Vol 59 (4) ◽

pp. 440-446 ◽

Cited By ~ 19

Author(s):

A. G. Pinto ◽

J. Horlander ◽

N. Chalasani ◽

M. Hamman ◽

A. Asghar ◽

...

Keyword(s):

Cytochrome P450 ◽

Cyp3a Activity ◽

Cytochrome P450 3A

Download Full-text

Drug interactions with grapefruit

Medicinski pregled ◽

10.2298/mpns1012805b ◽

2010 ◽

Vol 63 (11-12) ◽

pp. 805-810 ◽

Cited By ~ 2

Author(s):

Zoran Bojanic ◽

Novica Bojanic ◽

Vladmila Bojanic

Keyword(s):

Cytochrome P450 ◽

Drug Interactions ◽

Grapefruit Juice ◽

Pharmacokinetic Interaction ◽

Intestinal Wall ◽

Citrus Paradisi ◽

Citrus Fruits ◽

Inhibitory Effects ◽

Cytochrome P450 Isoenzyme ◽

Harmful Effects

Introduction. The concentration of many orally given medications may be affected by grapefruit or grapefruit juice consumption. It may result in numerous harmful effects. Interaction of grapefruit with drugs. Taking only one cup of juice may induce interactions with different drugs even during the period of a few days. The effect is induced by suppression of cytochrome P450 isoenzyme CYP3A4 in the intestinal wall. The Latin name of grapefruit, Citrus paradisi, is quite opposite to the effects which could be induced by taking grapefruit and some medications at the same time. It is necessary to avoid taking grapefruit with the drugs whose pharmacokinetics could be altered by the active principles found in that fruit. Discussion. The coloured grapefruit contains less furanocoumarins, but there is no difference in induction and intensity of pharmacokinetic interaction with drugs related to its colour. Other citrus fruits (orange, lemon) do not have such effects, but some other fruits (pomegranate, stella fruit, banpeiyu, hassaku, takaoka-buntan and kinkan) exert inhibitory effects on the activity of cytochrome P450 isoenzyme.

Download Full-text