Advice please, need help

[little men]

I have just found out medicine i am taking call cipramil anti depresant doesnt mix with nolvadex and i will be running armidex .5eod throughout my cycle of 8 weeks test prop 100mg eod / dbol 30mg daily and t3,

I cant use clomid as it makes my eyes blurry and am wondering is their a protocol for an armidex only pct and is this effective?

how would i dose it? any advice is appreciated

Thank you

[Lemonada8]

cipramil decreases the effectiveness of nolvadex by inhibiting its metabolism in the liver.

You could still take the nolva, but it may not be as effective.

What was your clomid dose? you could try taking a lower amount (50mg)

Armidex only for a pct isnt a wise idea, you can get a rebound. If you are going to use an AI for pct, then aromasin is a better choice. But aromasin doenst have the same actions as nolva/ clomid do which make them better for PCT.

[jimmyinkedup]

Does the same interaction occur with toremifene ? If not id recommend that.
Actually I recommend you wait for Swifto's input. He has a great grasp on variousp pct protocols.

[Lemonada8]

^^ good call Tore looks like it would be a good repla***ent
( i dont get the *** ? ) so... Alternative?

Background: Tamoxifen (TAM) is widely used as endocrine therapy for estrogen receptor (ER) positive breast cancer despite a growing controversy regarding its effectiveness in patients with compromised cytochrome P450 2D6 (CYP2D6) activity. Since it is metabolized to active metabolites via CYP2D6, legitimate concerns have been raised over concurrent use of TAM and drugs that are potent inhibitors of CYP2D6 (e.g., SSRI antidepressants). Toremifene (TOR) is a structural analog of TAM that is approved for the treatment of metastatic breast cancer in postmenopausal women with ER positive or unknown tumors. TOR is primarily metabolized by CYP3A4, while CYP2D6 is thought to play a minor role in its metabolism. We examined the role of individual CYP isoforms in the metabolism of TOR and TAM to N-desmethyl (NDM), 4-hydroxy (4-OH) and 4-OH-N-desmethyl (4-OH-NDM) metabolites. Methods: The in vitro metabolism of TOR and TAM was investigated using human liver microsomes and recombinant CYP proteins. Samples were analyzed by LC-MS/MS. Results: N-demethylation is the primary metabolic pathway for both TOR and TAM. Similar levels of N-desmethyl metabolites were formed for both compounds. N-demethylation occurred by CYP2D6, 3A4 and 1A1 but not appreciably by the other six CYP isoforms tested. Specific inhibitors of CYP2D6 and 3A4 activity blocked N-demethylation. The 4‑OH and 4-OH-NDM metabolites of TAM, but not TOR, were observed when the parent drugs were incubated with the CYP2D6 isoenzyme. The formation of both 4-OH-tamoxifen and 4-OH-NDM-tamoxifen (endoxifen) were significantly inhibited by 2D6 inhibitors, including the SSRI antidepressant paroxetine. These results were corroborated by studies using human liver microsomes from poor, intermediate and extensive CYP2D6 metabolizers. Conclusions: Tamoxifen, but not toremifene, is a substrate for 4-hydroxylation by CYP2D6 in human liver microsomes. The metabolism of toremifene is not markedly affected by potent CYP2D6 inhibitors in human liver microsomes. These results suggest that clinical benefit in subjects taking toremifene to treat metastatic breast cancer would not be subject to allelic variation in CYP2D6 status or affected by co-administration of CYP2D6-inhibiting medications.

Cipramil is a CYP2D6 inhibitor, which also metabolizes nolvadex hence the lowering of effectiveness of nolva.

[little men]

thanks, clomid 50mg was the dose with 40mg nolva my last pct, should i run the nolva at 60mg 2 weeks then 30mg 2 weeks and run the armidex at .25mg for the first week of pct?

[Lemonada8]

no go with tore instead at 120mg ED for 2 weeks then 60mg ED for 3 weeks.
And try 25mg clomid for 3 weeks since u have issues at a higher dose
no armidex in pct

[little men]

id prefer not to have to buy more pct as I have a load of nolvadex , if its a non negotiable then ill buy what you are reccomending.

im on 10mg cipramil daily which is low hence why im suggesting higher dose nolva to compensate. what are your views on this? am i playing around too much taking this risk?

thank you for your time

[Lemonada8]

doing that much nolva could work, but usually that much isnt good for someone anyways, esp a male.

I would go with Tore instead or wait untill you are done with the SSRI

[Swifto]

^^ good call Tore looks like it would be a good repla***ent
( i dont get the *** ? ) so... Alternative?



Cipramil is a CYP2D6 inhibitor, which also metabolizes nolvadex hence the lowering of effectiveness of nolva.

You're correct.

Tamoxifen isnt just metabolised by CYP2D6 however, its also metablized heavily in the liver by (wait for it) the CYP3A, CYP2D6, CYP2C9, CYP2C19, CYP2B6, and CYP1A2. So who's to say if one CPY enzyme is inhibited, the others will follow suit? Less effective (38-58% less).

For your information, the two most important isoforms responsible for Tamoxifen metabolism are the CYP3A enzyme (responsible for the formation of N-desmethyltamoxifen) and the CYP2D6 (for 4-hydroxytamoxifen and endoxifen).

I'll quote from the study I will post at the bottom of this page.

Effect of CYP2D6 Inhibitors on Plasma Concentrations of Endoxifen

The plasma endoxifen concentrations in patients who were homozygous for the wild-type allele were highly variable (Fig. 3, A). Although rare variants in the CYP2D6 gene might have contributed to this large interindividual variability, it was also possible that the variability was due to exposure to drugs that inhibit the CYP2D6 enzyme. To test this latter possibility, we examined the association between the use of known CYP2D6 inhibitors and mean plasma endoxifen concentration. In our cohort of 80 breast cancer patients, 78 women had complete medication records 4 months after they had initiated tamoxifen therapy; of these, 24 women (30.8%) were taking medications considered to be CYP2D6 inhibitors based on results of published drug interaction studies (www.drug-interactions.com), including paroxetine, fluoxetine, sertraline, citalopram, amiodarone, and metoclopramide. Among subjects who carried the Wt/Wt genotype, the mean plasma endoxifen concentration for those who were using CYP2D6 inhibitors was 58% lower than that for those who were not using CYP2D6 inhibitors (38.6 nM versus 91.4 nM, difference = –52.8 nM, 95% CI = –86.1 to –19.5 nM, P = .0025) (Fig. 3, B). Among subjects who were heterozygous for a nonfunctional CYP2D6 allele (i.e., the Wt/Vt group), the mean plasma endoxifen concentration for those who were using CYP2D6 inhibitors was 38% lower than that for those who were not taking CYP2D6 inhibitors (31.0 nM versus 51.7nM, difference = –20.7 nM, 95% CI = –42.7 to 1.31 nM, P = .08) (Fig. 3, B). Only three subjects were homozygotes for the CYP2D6*4/*4 genotype, and none of those three subjects was taking CYP2D6 inhibitors. Among the 54 subjects who were not taking a CYP2D6 inhibitor concomitantly with tamoxifen therapy, plasma concentrations of endoxifen were associated with the CYP2D6 genotype, as shown in Fig. 3, B (P = .0001). Among subjects who were taking CYP2D6 inhibitors, there was no statistically significant difference in the mean plasma concentration of endoxifen between subjects with the CYP2D6 Wt/Wt and Wt/Vt genotypes (38.6 nM versus 31.0 nM, difference = 7.6 nM, 95% CI = –6.2 to 21.4 nM, P = .45).

Study

Thats was a reply I posted at OLM. The OP stated its "useless" over there before I corrected him.

[little men]

the only place i know to get liquid torem is out of stock,
if i cant get it by the time i need to do pct would 80mg for two weeks and 40mg for two weeks be ok to compensate for the reduction in effectivness????

thanks again