[peggy]

Thanks Lotus.

[Lotus]

Thanks Lotus.

Oh wait there's more, it's more of a hepatic metabolism response or attempt then called a second pass, but for our purposes that's what we mean.

One process results in a reduced amount of drug that the body actually ends up utilizing; the other results in an increase in the amount of drug that the body ends up utilizing. Here's how:

First pass metabolism is what occurs when a drug is absorbed from the GI tract. When a drug is taken orally it is absorbed into the portal circulation (the blood vessels of the liver). Many of these drugs are very efficiently metabolized (altered for elimination) as they pass through the portal circulation during this first time. It reduces the amount of active drug that gets into the general circulation. This is first-pass metabolism.

Enterohepatic cycling is where:
Unmetabolized drugs as well as drug metabolites go through the liver and biliary tract for excretion and proceed to make their way out of the body through the intestinal tract. In other words, this is the body's way of putting them in the trash and getting rid of them.
Here's the catch. . .on the way out through the intestines (the entero part of the word enterohepatic) some of the discarded active drug gets reabsorbed back into the blood stream where it is again available to the body for use. In other words, it's being recycled.
RESULT: The half life and duration of action of a drug is increased.

First-pass elimination. Basic concepts and clinical consequences.
http://www.ncbi.nlm.nih.gov/pubmed/6362950

http://wikipedia.org/wiki/First_pass_effect

Drug metabolism
http://en.wikipedia.org/wiki/Drug_metabolism

[EvaMarie]

Thanks Lotus, Im starting to get this I think (I'll try to avoid my blonde wig for a while LOL)

Guess who is going to learn to love grapefruit juice and the fruit itself for breakfast with some oatmeal whether she likes it or not

I found this, thought it was interesting, its EE2 (synthetic not bio identical E2) designed to intentionally be harder to eliminate from the body (potent stuff) nevertheless less Id think the same would apply to E2 whether aromatitzed naturally with NBE or taken in pharma form....

The effects of grapefruit juice on the bioavailability of 17 alpha-ethinylestradiol (EE2) after a single oral administration of 50 micrograms EE2 have been investigated. The pharmacokinetics of EE2 were studied in an open, randomized, cross-over study in which 13 healthy volunteers were administered the drug with herbal tea or grapefruit juice (naringin, 887 mg/ml). In contrast to herbal tea, grapefruit juice increased the peak plasma concentration (Cmax) significantly to 137% (mean; range 64% to 214%, p = 0.0088) and increased the area under plasma concentration-time curve from 0 to 8 hours (AUC0-8) to 128% (mean; range 81% to 180%, p = 0.0186). This study shows that grapefruit juice increases the bioavailable amount of EE2. A possible explanation may be that grapefruit juice inhibits the metabolic degradation of EE2. Whether the increased bioavailability of EE2 following grapefruit juice administration is of clinical importance should be investigated in long-term studies.

http://www.ncbi.nlm.nih.gov/pubmed/8631189

More on grapefruit juice and drug interactions including E2

http://www.alsclinic.com/english/DrugAdm...tJuice.pdf

http://www.livestrong.com/article/108077...rapefruit/

[EvaMarie]

Very interesting

Grapefruit juice inhibits drug metabolism at the GI tract, so its effects on estrogen would be most pronounced with oral dosage forms, leading to increased levels of estrogens in the bloodstream. We are recommending that women stay away from oral estrogens in most cases so that would help diminish any potential interactions, however, estrogens are enterohepatically recirculated (the estrogens circulate through the bile duct, through the GI tract and back into the circulation) so even with topical administration, there may be some effect. Of course, I recommend that women have their estrogen levels tested whenever they are on supplementation, and if a patient is having an interaction with grapefruit juice, it would be picked up as higher levels.

So, should women who are on transdermal estrogens avoid grapefruit juice? I guess it’s probably a good idea, but not an absolute.

Estrogen and progestin combination: Grapefruit may increase the bioavailability and side effects associated with estrogen (153; 154; 155). In one randomized crossover trial, grapefruit juice increased the ethinylestradiol Cmax significantly to 137% (p=0.0088) and increased the AUC(0-8) to 128% (p=0.0186) (155). Grapefruit juice has demonstrated the ability to alter the metabolic degradation of estrogens and increase the bioavailable amounts of 17beta-estradiol and its metabolite estrone in ovariectomized women (154). The most likely mechanism of action of the flavonoids of grapefruit juice on 17 beta-estradiol metabolism is the inhibition of the CYP450 3A4 enzyme, which catalyzes the reversible hydroxylation of 17 beta-estradiol into estrone and further into estriol (154).

http://www.menopausetheblog.com/2011/03/...re-on-hrt/