and found conflicting data:
1)
http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum
Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice.
2)
Quote:
Drug Metab Dispos. 2007 Feb;35(2):302-5. Epub 2006 Nov 28.Click here to read Links
Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.
Nagata M, Hidaka M, Sekiya H, Kawano Y, Yamasaki K, Okumura M, Arimori K.
School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka City, Miyazaki, 882-8508, Japan. m-nagata@phoenix.ac.jp
In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4'-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9. The addition of 25 microl (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In addition, we investigated the effect of pomegranate juice on the pharmacokinetics of tolbutamide (substrate for
) in rats. Relative to the control group, the area under the concentration-time curve was approximately 1.2-fold greater when pomegranate juice (3 ml) was injected p.o. 1 h before the p.o. administration of the tolbutamide (20 mg/kg). The elimination half-life of tolbutamide was not altered by pomegranate juice administration. These results suggest pomegranate juice ingestion inhibits the intestinal metabolism of tolbutamide without inhibiting the hepatic metabolism in rats. Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.
PMID: 17132763 [PubMed - indexed for MEDLINE]
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Only problem here is tolbutamide is not used much anymore.
3) here is a handy chart showing various metabolic pathways:
http://www.healthanddna.com/drugchart.html
The one for pomegranate juice is CYP2C9
Remember, that lists like this are subject to change.
Here is a chart just for grapefruit juice:
http://www.fhma.com/grapefruit.htm
4) here is a paper giving relative potency/effects of various juices:
Quote:
Drug Metab Dispos. 2006 Apr;34(4):521-3. Epub 2006 Jan 13.Click here to read Links
Inhibitory effects of fruit juices on CYP3A activity.
Kim H, Yoon YJ, Shon JH, Cha IJ, Shin JG, Liu KH.
Department of Pharmacology, Inje University College of Medicine, # 633-165, Gaegum-Dong, Jin-Gu, Busan 614-735, South Korea.
There have been very limited reports on the effects of commercial fruit juices on human CYP3A activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum, and wild grape. White grapefruit, pomegranate, and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC(50) values of all fruit juices tested were reduced after preincubation with microsomes in the presence of the NADPH-generating system, suggesting that a mechanism-based inhibitory component was present in these fruit juices, as in the case of grapefruit. The results suggest that, like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant.
PMID: 16415112 [PubMed - indexed for MEDLINE]
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5) And there is a difference between enteric enzymes and liver enzymes:
Quote:
Drug Metab Dispos. 2005 May;33(5):644-8. Epub 2005 Jan 26.Click here to read Links
Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats.
Hidaka M, Okumura M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Setoguchi N, Arimori K.
Department of Pharmacy, Miyazaki Medical College Hospital, Kiyotake-cho, Miyazaki-gun, Japan. yshidaka@med.miyazaki-u.ac.jp
In this study, we investigated whether components of pomegranate could inhibit CYP3A-mediated drug metabolism. The ability of pomegranate to inhibit the carbamazepine 10,11-epoxidase activity of CYP3A was examined using human liver microsomes, and pomegranate juice was shown to be a potent inhibitor of human CYP3A. Addition of 25 microl (5.0% v/v) of pomegranate juice resulted in almost complete inhibition of the carbamazepine 10,11-epoxidase activity of human CYP3A (1.8%). The inhibition potency of pomegranate juice was similar to that of grapefruit juice. In addition, we investigated the in vivo interaction between pomegranate juice and carbamazepine pharmacokinetics using rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.5-fold higher when pomegranate juice (2 ml) was orally injected 1 h before the oral administration of the carbamazepine (50 mg/kg). On the other hand, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the injection of pomegranate juice. These data suggest that pomegranate juice component(s) impairs the function of enteric but not hepatic CYP3A. Thus, we discovered that a component(s) of pomegranate inhibits the human CYP3A-mediated metabolism of carbamazepine. Furthermore, pomegranate juice alters the carbamazepine pharmacokinetics in rats.
PMID: 15673597 [PubMed - indexed for MEDLINE]
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And there is some concern that data is not forthcoming in humans as much as rats. There may be differences there too.
It took a LONG time for data to be compiled on grapefruit juice. Since pomegranate has become popular, it will take a long time to get really good data on that one too. Since there is not a definitive answer it is best to avoid pomegranate if you are on Rx medications.
This link explains some of the above PubMed papers into clear English:
http://www.netwellness.org/question.cfm/44966.htm
I wonder how much a doctor really knows or understands about complex drug metabolism, so it is best if YOU look up stuff as well yourselves. I have found many doctors rather clueless on this topic.
And of course the studies do not include data on genetically "slow metabolizers". These are people who don't metabolize drugs like the majority.
In response to the article that fibrowendy posted about Crestor and Zetia... Crestor has been found to not
be metabolized normally in genetically "slow metabolizers". This includes many Asians, and about 10% of the rest of the
population. Many people had toxicity from Crestor until FDA sent out letters to doctors to LOWER doses in this
group or not use this drug. So that may be a factor in that report.
Crestor is the most toxic statin, and during trials there were deaths on it....a rare event. So I suspect some additive
situation with it.
I personally don't think pomegranate juice is going to be a
huge problem, but something to watch in any event.
__________________
All truths are easy to understand once they are discovered; the point is to discover them.-- Galileo Galilei
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Weezie looking at petunias 8.25.2017
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