After discussing Cytochrome P450 (superfamily of enzymes) in my pharmacology class ive been looking into the affects of grapefruit on it. Grapefruits essentially decrease cytochrome P450 increasing the bioavailability of certain drugs. P450 also plays a role in aromatase, so if you inhibit P450, from what I can tell you would inhibit aromatase? Can anyone confirm if this is correct? a subset of P450 also plays a role in steroidogenesis, so if grapefruit inhibits P450, are you also inhibiting steroidogenesis?
Basically is the aromatase inhibitory effects of grapefruit worth reducing steroidogenesis? probably not but I’d like to hear other people’s opinion on this who have a better understanding of it than I do.
[quote]bushidobadboy wrote:
Overloading the CYP pathway will cause a buildup of estrogen and estrogen metabolites in the system. Not something you really want.
Aromatisation occurs chiefly in visceral adipose tissue, not the liver and the CYP450 familly is predominantly active in the liver, so I’m not at all sure that your analysis of aromatase Vs CYP450 is correct.
BBB[/quote]
Damn, how do you know something off the wall like this? I’m assuming you’re educated. What studies did you concentrate in?
[quote]absolute3 wrote:
The only thing grapefruit is good for is potentiating opiates and some other drugs. That, and it tastes fucking great :)[/quote]
right. this is what began my research into it. I was looking into whether the reduction in steroidogenesis would be a reasonable tradeoff for increasing bioavailability of oral steroids or possibly prohormones. the thing with prohormones though is some dont become active until they are metabolized in the liver, so inhibiting p450 may actually decrease bioavailability of some prohormones and prodrugs?
[quote]bushidobadboy wrote:
It won;t work on cocaine since that has such poor oral bioavailability that nobody takes it that way.[/quote]
I assume you are referring to nasal insufflation? My understanding is that although some of the cocaine is absorbed via the mucus membrane, most of it ends up in the back of the throat and then eventually the stomach–essentially taking the same path as oral administration.
[quote]bushidobadboy wrote:
Whilst I’m here, I would like to point out that large doses of vitamin C will have the opposite effect to grapefruit juice, de-loading the CYP450 pathway, aiding clearance of drugs, estrogen, etc.
BBB[/quote]
So does St. John’s Wort. The problem is that “de-loading the CYP450” pathway itself can induce certain problems with OTHER drugs that are easily made more soluble by Phase I enzymes such as Cyclosporine (used to prevent rejection in organ transplantation), protease inhibitors, MAO inhibitors, certain antidepressants, etc. Also more CYP450 is not necessarily good and less is not necessarily bad (in healthy individuals), as CYP450 often actually converts perfectly harmless compounds into more toxic ones (example would be benzopyrene or acetaminophen).
Ok, thats all great, but what about the molecular phase transfusion that is initiated by the high quantities of glucocortoids as a result of the citroflavinoids of the grapefruit passing through the iliotibial ducts of the pancreas? The resulting cascade of disulfates and dendrites into the bloodstream surley has to be accounted for in some way?
