Any Non-Responders Out There?

**guest589745** · 09-23-2006, 01:41 PM

RTV/Norvir/Ritonavir can result in a 2x-3x build-up of anabolics in blood.

Good site for drug interactions http://www.thebody.com/asp/apr03/risky_cocktails.html

**Warrior21** · 09-23-2006, 01:41 PM

SKull were speaking the same language. If we can inhibit the CYP P450 enzymes we can use less gear and have higher amounts in our blood! It's all starting to make sense!
Remember I said my brother just started responding to gear about 2 years ago? Well I asked my mother how long he has been getting allergy shots. Guess how long? 2 years! This is it bro. Antihistamines are CYP P450 inhibitors! Do you take antihistamines at all? I'm thinking of researching some antihistamines and then cycling Anavar /Antihistamine! This is it bro!

**Warrior21** · 09-23-2006, 01:47 PM

Skull don't get discouraged, we got it. This has to be our case. Look I notice that just 5 minutes after Taking Anavar my body gets a slight pump, it always happens! So what is going on? My body is metabolising Anavar super fast! It's probably only in my blood for 2-3 hours a day total. How do we get more anabolics in our blood by taking less? Grapefruit juice, Norvir, Antihistamine.

C'mon we gotta try something. My brother gets antihistamine injections once a month. I bet they are definately inhibiting his naturally high levels of
CYP P450, therefore he can now gain on steroids ? He's responding remarkably well on just 60mg a day.

Plenty of people have been telling me that he is bullshitting me. The truth to it has to be that the fact that his CYP P450 is inhibited so his bioavailability of Oxandrolone must be superior.

**guest589745** · 09-23-2006, 01:55 PM

I hope we are on to something.........

I would like to hear othe rmembers opinions as well.

**Warrior21** · 09-23-2006, 01:58 PM

Yea there's a few members looking at the thread right now. Feel free to chime in.

Skull I'm 99% sure this is my case at least. And if it all adds up it helps you anyways, now you don't have to mega-dose on steroids . I read up on Norvir and it seems pretty dangerous. Maybe a light, light dose would do the trick. Of course for good measure start taking grapefruit juice with your orals.

Check this Wiki out on CYP P450, there's a list of inhibitors on here that would do us good. I'm going to be researching most, if not all of them. Lets find the safest one for us.

http://en.wikipedia.org/wiki/CYP2D6

**stupidhippo** · 09-23-2006, 02:06 PM

how are AAS metabolized? is it throught the cyt P450 system or not? and to what extenT? It didnt say how does ritonavir etc increase blood concentrations of anabolics... This is indeed interesting but Im warning not to make too quick assumptions... this stuff is actually alot more complex than it seems..

**guest589745** · 09-23-2006, 02:06 PM

This is interesting as well

http://www.gfmer.ch/Books/Reproducti...etabolism.html

also claritin inhibits CYP2D6.

**guest589745** · 09-23-2006, 02:07 PM

Originally Posted by stupidhippo

This is indeed interesting but Im warning not to make too quick assumptions... this stuff is actually alot more complex than it seems..

Definately.

**Warrior21** · 09-23-2006, 02:09 PM

CYP P450 is responsible for metabolising drugs. And whether you beleive it or not injectible drugs pass through the liver too. An increase in anabolics in the blood is crucial, no matter how it is accomplished.

Call me crazy but I'm going to come up with a solution for this shit. I'm not going on for the rest of my life not responding to AS. There's too many other things that suck for me which I cannot do anything about, but this... I'm going to solve.

**guest589745** · 09-23-2006, 02:11 PM

Originally Posted by stupidhippo

how are AAS metabolized? is it throught the cyt P450 system or not? and to what extenT? ..

The first committed step in steroid biosynthesis is the conversion of the 27-carbon skeleton of cholesterol to a C21-compound, pregnenolone (Fig. 2). This critical step, which is subject to hormonal control by the adrenocorticotropic hormone (ACTH) in the adrenals and by the luteinizing hormone (LH) in the gonads, is catalysed by a P-450 enzyme, the cholesterol side-chain cleavage enzyme P-450scc (also called 20,22-desmolase, or 20,22-lyase).

Does this answer that ?

**stupidhippo** · 09-23-2006, 02:13 PM

gonna read that article later.. now gotta run... whaty it seems like is thouh that cyt 450 wouldnt play a very big role in deactivating AAS.. some one either confirm or correct me..

**stupidhippo** · 09-23-2006, 02:15 PM

Originally Posted by Skullsmasher

The first committed step in steroid biosynthesis is the conversion of the 27-carbon skeleton of cholesterol to a C21-compound, pregnenolone (Fig. 2). This critical step, which is subject to hormonal control by the adrenocorticotropic hormone (ACTH) in the adrenals and by the luteinizing hormone (LH) in the gonads, is catalysed by a P-450 enzyme, the cholesterol side-chain cleavage enzyme P-450scc (also called 20,22-desmolase, or 20,22-lyase).

Does this answer that ?

no since that is in the synthesis.. when we inject the hormones we dont have to worry about that part.. but it didnt come clear to me weather it is active in the catabolism / metabolism of the hormones in question.. also AAS can differ in pharmacokinetical properties from test for example...

**guest589745** · 09-23-2006, 02:17 PM

Supposedly polynsaturated fats inhibit CYP2D6 so maybe this is why high fat diets increase testosterone ...??

**Warrior21** · 09-23-2006, 02:19 PM

CYP P450 pretty much dominates metabolism of all drug (xenobiotics). Some people are ultrarapid metabolisers (most likely me). I read one study on a drug with a 22 hour half life and an ultrarpid metaboliser passed it in 2-4 hours they said.

My hypothesis on my situation is that I'm taking Anavar (9-12 hour half life) and it may be out of my system within 1-2 hours of taking it. A steroid cannot do shit for you if it is only in your body 3-4 hours a day. Hence I'm looking into inhibitors for this hepatic enzyme. Beleive it or not there are plenty of common medications which do inhibit it. You guys may be on one, and consequently respond extra well to AS. Due to the fact that I am young and in good health... I don't have a need for any medications. Will I take a light dose of medication I don't need when I start a cycle? Hell yes. I want it that bad, can you blame me?

**Warrior21** · 09-23-2006, 02:20 PM

Originally Posted by Skullsmasher

Supposedly polynsaturated fats inhibit CYP2D6 so maybe this is why high fat diets increase testosterone...??

I don't know that one, all I can tell you is that when I used high olive oil diets back in the day (Doggcrapp methods) I always had an oily forehead. My test was definately raised by polyunsaturateds.

Dude we are onto something here.

**stupidhippo** · 09-23-2006, 02:22 PM

while ur idea is tempting I pretty much doubt it... to my understanding p450 is not active in all metabolism (of all drugs).. and also with the manipulation of p450 activation usually not such drastic difference is seen.

**Warrior21** · 09-23-2006, 02:25 PM

Upon further reflection. I'm damn sure that I'm metabolising these AS too fast. I would have ran into trouble when I was younger fking with compounds like Fina. My test has never been shut down guys. The stuff is just not getting into my blood. The little bit that is getting into my blood is leaving me within a few hours.
My mother had me tested for steroids when I was younger, I never tested positive for anything, even while I was on. Maybe they didn't test for thw compounds I was on. Just some food for thought.

Anyways I'm going to dinner with the family and girl. I'll be back in a couple hours. Have fun researching Skull! I'll talk to ya later guys. Thanks for your help and support.

**Warrior21** · 09-23-2006, 02:25 PM

Upon further reflection. I'm damn sure that I'm metabolising these AS too fast. I would have ran into trouble when I was younger fking with compounds like Fina. My test has never been shut down guys. The stuff is just not getting into my blood. The little bit that is getting into my blood is leaving me within a few hours.
My mother had me tested for steroids when I was younger, I never tested positive for anything, even while I was on. Maybe they didn't test for thw compounds I was on. Just some food for thought.

Anyways I'm going to dinner with the family and girl. I'll be back in a couple hours. Have fun researching Skull! I'll talk to ya later guys. Thanks for your help and support.

**Warrior21** · 09-23-2006, 02:27 PM

Originally Posted by stupidhippo

while ur idea is tempting I pretty much doubt it... to my understanding p450 is not active in all metabolism (of all drugs).. and also with the manipulation of p450 activation usually not such drastic difference is seen.

Did you read the part about my brother and the antihistamines he's on? He started responding to AS right around the same time he started his Allergy injections bro. Can't be just a coincidence. Anyways I'll be on later.

**guest589745** · 09-23-2006, 02:29 PM

Originally Posted by stupidhippo

while ur idea is tempting I pretty much doubt it... to my understanding p450 is not active in all metabolism (of all drugs).. and also with the manipulation of p450 activation usually not such drastic difference is seen.

what are you refering to ?

**stupidhippo** · 09-23-2006, 02:32 PM

just what Ive been taught... but I could remember wrong.. also Im saying to warrior not to get discouraged by me but most probably his sitaution aint as simple as this..

with the p450 comment... think of all the medication that inhibits it, there are plenty. Anyone ppl who would be using those medications would be in problematic situation if the effect was always so drastic.. with some drugs the interactions can be drastic indeed.. but not all, even if they are effected by the P450 system..

**stupidhippo** · 09-23-2006, 02:33 PM

Originally Posted by Warrior21

Did you read the part about my brother and the antihistamines he's on? He started responding to AS right around the same time he started his Allergy injections bro. Can't be just a coincidence. Anyways I'll be on later.

if the same works for u maybe u are on to something.... Im not saying u are wrong.. Im just saying its unlikely that u are right.... but keep us posted. Im interested..

**stupidhippo** · 09-23-2006, 02:36 PM

ive been on anti histamines and gear the same time and no noticable differences... but there are thousand possible explanations.. if it worked for youer brother maybe it works for u..

**cfiler** · 09-23-2006, 02:45 PM

Originally Posted by Warrior21

Did you read the part about my brother and the antihistamines he's on? He started responding to AS right around the same time he started his Allergy injections bro. Can't be just a coincidence. Anyways I'll be on later.

Nope, I respond extreamly well to anabolic or androgenic compounds and I use antihistamines all the time. While on cycle and off.

**stupidhippo** · 09-23-2006, 02:46 PM

Originally Posted by Warrior21

Upon further reflection. I'm damn sure that I'm metabolising these AS too fast. I would have ran into trouble when I was younger fking with compounds like Fina. My test has never been shut down guys. The stuff is just not getting into my blood. The little bit that is getting into my blood is leaving me within a few hours.
My mother had me tested for steroids when I was younger, I never tested positive for anything, even while I was on. Maybe they didn't test for thw compounds I was on. Just some food for thought.

Anyways I'm going to dinner with the family and girl. I'll be back in a couple hours. Have fun researching Skull! I'll talk to ya later guys. Thanks for your help and support.

this is indeed interesting.. if this is true there is obviously some reason y the gear aint working with u.... is it being deactivated and if so by what mechanism...

**guest589745** · 09-23-2006, 05:08 PM

Bump for more replies.

anyone know of DMMS? Drug microsomal metabolizing sys?

**taiboxa** · 09-23-2006, 06:40 PM

Ok i dont have much time but i did get MANY PM's kuz of this thread LOL
and i have an explanation that can answer all those who have very lil gains from moderate doses of aas even when diet/training is 100000% on top of the gonad.

after taking 4 different pharmacology courses i have come to the conclusion that there are many people out there that have a HYPER DMMS which is like those who have Hyperthyroidism or hyperglycemia or wat not..

Ur DMMS is ur drug microsomal metabolizing system, it is what determines the break down rate of all drugs in the system and is not exclusive to hormones. since it is an exogenous substance, that is all i could conclude from the studies i have done/conducted on this subject...

(as followup im doing a study on the DMMS for my Sr. Research subject and i will be conducting my proposal infront of an assload of dr.'s in 3 weeks (NERVOUS AS ****))

now there are many underlying factors that affect this but the 3 big main ones that we can control ... TO AN EXTENT are
Your LBM/Size
Your metabolism
and drug exposure/dose all 3 are common sense DUH!
if u use a DRUG consistently YOUR BODY will adapt this is true w/ aas though there are some non believers out there
so to beat our DMMS we have to calculate our doses accordingly to the preceding factors

Keep upin a dose till u get results
CHANGE the substance u run each time NEVER use the same oral in back to bak runs
keep test low its weak use the big Nor's and DHTs to do ur dirty work and KEEP SWAPPING THEM if u run win one time for dht use drol next tim eor mast
for nors swap between tren and deca
every now and then use some halo/dbol to mix shit up and PRAY PRAY PRAY LOL
THATS ALL I GOT RIGHT NOW if u want more info i suggest u go buy some books on it or take a few pharm courses, also i typed this in like 2min proly lots of errors and doesnt make much grammarical sense PLEASE TRY DO TO UR BEST AND REMEMBER I HAVE ADHD AND DYSLEXIA!

**taiboxa** · 09-23-2006, 09:48 PM

Originally Posted by Warrior21

CYP P450 pretty much dominates metabolism of all drug (xenobiotics). Some people are ultrarapid metabolisers (most likely me). I read one study on a drug with a 22 hour half life and an ultrarpid metaboliser passed it in 2-4 hours they said.

My hypothesis on my situation is that I'm taking Anavar (9-12 hour half life) and it may be out of my system within 1-2 hours of taking it. A steroid cannot do shit for you if it is only in your body 3-4 hours a day. Hence I'm looking into inhibitors for this hepatic enzyme. Beleive it or not there are plenty of common medications which do inhibit it. You guys may be on one, and consequently respond extra well to AS. Due to the fact that I am young and in good health... I don't have a need for any medications. Will I take a light dose of medication I don't need when I start a cycle? Hell yes. I want it that bad, can you blame me?

LOL hit me up w/ the compounds u have ran and wat doses and duration.
i gurantee u we kan get something to happen... but we are exactly in the same boat.. painkillers and shit dont have much more than a 30min window of euphoria while most shud exhint anywhere from 3-6hrs depending on dose.

**taiboxa** · 09-23-2006, 10:38 PM

oh hey i would like to just say that any smart people out there big into doing diligent free research wanna get together w/ me and maby create a lil article on how to dose accordingly to one's dmms?
sounds fun to me!

**guest589745** · 09-23-2006, 11:14 PM

Originally Posted by taiboxa

Ok i dont have much time but i did get MANY PM's kuz of this thread LOL
and i have an explanation that can answer all those who have very lil gains from moderate doses of aas even when diet/training is 100000% on top of the gonad.

after taking 4 different pharmacology courses i have come to the conclusion that there are many people out there that have a HYPER DMMS which is like those who have Hyperthyroidism or hyperglycemia or wat not..

Ur DMMS is ur drug microsomal metabolizing system, it is what determines the break down rate of all drugs in the system and is not exclusive to hormones. since it is an exogenous substance, that is all i could conclude from the studies i have done/conducted on this subject...

(as followup im doing a study on the DMMS for my Sr. Research subject and i will be conducting my proposal infront of an assload of dr.'s in 3 weeks (NERVOUS AS ****))

now there are many underlying factors that affect this but the 3 big main ones that we can control ... TO AN EXTENT are
Your LBM/Size
Your metabolism
and drug exposure/dose all 3 are common sense DUH!
if u use a DRUG consistently YOUR BODY will adapt this is true w/ aas though there are some non believers out there
so to beat our DMMS we have to calculate our doses accordingly to the preceding factors

Keep upin a dose till u get results
CHANGE the substance u run each time NEVER use the same oral in back to bak runs
keep test low its weak use the big Nor's and DHTs to do ur dirty work and KEEP SWAPPING THEM if u run win one time for dht use drol next tim eor mast
for nors swap between tren and deca
every now and then use some halo/dbol to mix shit up and PRAY PRAY PRAY LOL
THATS ALL I GOT RIGHT NOW if u want more info i suggest u go buy some books on it or take a few pharm courses, also i typed this in like 2min proly lots of errors and doesnt make much grammarical sense PLEASE TRY DO TO UR BEST AND REMEMBER I HAVE ADHD AND DYSLEXIA!

Thanks tai!!!!!!! Thats exactly what I was thinking, test IS weak. I may speak with you in the future when you have time.

**Warrior21** · 09-24-2006, 07:47 AM

Okay guys i tried to get back on yesterday but couldn't. heh family offered to go watch a movie but I was like "No, I gotta research!". Coulnd't get on "Cannot find server kept popping up".

Anyways check this link;
http://aidsinfonyc.org/hivplus/issue1/ahead/p450.html

This one too;
http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=7764457

THE MAIN P450 that metabolizes AAS is CYP 3a4. There are many compounds that inhibit CYP 3A4, grapefruit juice even inhibits it. Right now I'm taking my Var with grapefruit juice. I'm thinking of doing 150mg Var and see if I get results from it. Maybe I will take doses every 2-3 hours. Dude this is a pain in the ass. There has to be a solution for this.

Thanks Tai for all your help, Skull of course, and for all the other guys who had their say in this.

PS. To the guy who uses antihistamines on cycle, so you think the antihistamines didn't have anything to do with my brother responding? Damn what could it be then. He was just like me, now he's responding good. I have to have a long interrogation with him lol.

**Warrior21** · 09-24-2006, 07:51 AM

Cytochrome P450 and drug interactions

Cytochrome P450: genetic polymorphism and drug interactions.Belpaire FM, Bogaert MG.
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.

In this review, after a short discussion of our knowledge about cytochrome P450 isoenzymes, two important sources of variability in the metabolism of drugs by cytochrome P450 are described, i.e. genetic factors and drug-drug interactions. Many hepatic cytochrome P450 enzymes play an important role in the oxidative biotransformation of numerous drugs and other foreign compounds, and of many endogenous substrates. In humans more than 20 different isoenzymes of cytochrome P450 responsible for the hepatic metabolism of drugs, have been identified. They are classified into families and subfamilies on the basis of the degree of amino acid similarity. Cytochrome P450 isoenzymes are regulated by both genetic and environmental factors. Of particular interest is genetic polymorphism in drug oxidation. Two genetic polymorphisms in drug oxidation are well known, the sparteine/debrisoquine (CYP2D6) polymorphism and the mephenytoin oxidation (CYP2C19) polymorphism. As a result of these polymorphisms, two phenotypes exist in the population, poor and extensive metabolizers. Poor metabolizers may be prone to adverse reactions towards drugs with a narrow therapeutic range. In extensive metabolizers clinically significant drug interactions between drugs metabolized by the same isoenzyme can occur.

PMID: 8858891 [PubMed - indexed for MEDLINE]

**Warrior21** · 09-24-2006, 07:53 AM

Grapefruit Juice Increases Bioavailability of CYP 3A4(steroid metabolising channel) metabolized drugs

Food-drug interaction: grapefruit juice augments drug bioavailability--mechanism, extent and relevance.Dahan A, Altman H.
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.

More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

PMID: 14679360 [PubMed - indexed for MEDLINE]

**guest589745** · 09-24-2006, 08:00 AM

Good info warrior.

**Warrior21** · 09-24-2006, 08:09 AM

I got alot more, I researched this when I got back last night for like 6 hours. Stayed up late. Barely could sleep. I don't think I'll rest any until we find out whats going on. I don't think I will end up having to go on 2 grams of test a week to get 500mg/weekly results you know. We will find a way around this so that we can take normal doses and respond like normal people.

**guest589745** · 09-24-2006, 08:17 AM

Originally Posted by Warrior21

I got alot more, I researched this when I got back last night for like 6 hours. Stayed up late. Barely could sleep. I don't think I'll rest any until we find out whats going on. I don't think I will end up having to go on 2 grams of test a week to get 500mg/weekly results you know. We will find a way around this so that we can take normal doses and respond like normal people.

I agree with what tai said in regards to running test low and keeping the nors/dhts higher to do the real work. I will be doing that in the future.

Have you read anymore on claritin inhibiting CYP34A or anythign else besides grapefruit juice ? The juice may be enough by itself, if not, I may try something else along with it that is mild first, but what.......

**guest589745** · 09-24-2006, 08:18 AM

See this statement right here makes it sound like thats all you need:

"A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction"

**Warrior21** · 09-24-2006, 08:25 AM

Yes it would seem that grapefruit juice can only do so much. But not everything is as it seems huh?

We can start with grapefruit juice. Heres another link that lists ALL the
CYP 3A4 inhibitors: http://en.wikipedia.org/wiki/CYP3A4

I've studied some, not just grapefruit juice. But they carry some heavy sides. Compound those sides on the sides from AS, it's no fun

But like I said I would do them either way, maybe just a smaller dose than for their real medical purposes. I wish I could get some allergy shots just like my bro and see if that works. He takes his once a month, but it's a slow release chemical they give him I guess. I'm going to have to see if he is taking other medications.

**guest589745** · 09-24-2006, 08:33 AM

Originally Posted by Warrior21

Yes it would seem that grapefruit juice can only do so much. But not everything is as it seems huh?

We can start with grapefruit juice. Heres another link that lists ALL the
CYP 3A4 inhibitors: http://en.wikipedia.org/wiki/CYP3A4

I've studied some, not just grapefruit juice. But they carry some heavy sides. Compound those sides on the sides from AS, it's no fun

But like I said I would do them either way, maybe just a smaller dose than for their real medical purposes. I wish I could get some allergy shots just like my bro and see if that works. He takes his once a month, but it's a slow release chemical they give him I guess. I'm going to have to see if he is taking other medications.

why wouldnt you be able to?

**guest589745** · 09-24-2006, 08:37 AM

try looking up how or if allergy meds such as claritin inhibit CYP3A4. I found this:

Metabolism: In vitro studies with human liver microsomes indicate that loratadine (Claritin) is metabolized to descarboethoxyloratadine predominantly by cytochrome P450 3A4 (CYP3A4) and, to a lesser extent, by cytochrome P450 2D6 (CYP2D6). In the presence of a CYP3A4 inhibitor ketoconazole, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6. Concurrent administration of loratadine with either ketoconazole, erythromycin (both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) to healthy volunteers was associated with substantially increased plasma concentrations of loratadine (see Drug Interactions section).