I don't care about a popularity contest. I graduated from HS over 20 years ago. I am here to let the community know people like hooker don't know shit. Him and his little gang can neg me all they want.
how about this study stating the 24 hr terminal half life and the 25mg optimal dosage?
Pharmacokinetics
Following oral administration to healthy postmenopausal women, exemestane is rapidly absorbed. After maximum plasma concentration is reached, levels decline polyexponentially with a mean terminal half-life of about 24 hours. Exemestane is extensively distributed and is cleared from the systemic circulation primarily by metabolism. The pharmacokinetics of exemestane are dose proportional after single (10 to 200 mg) or repeated oral doses (0.5 to 50 mg). Following repeated daily doses of exemestane 25 mg, plasma concentrations of unchanged drug are similar to levels measured after a single dose.
Pharmacokinetic parameters in postmenopausal women with advanced breast cancer following single or repeated doses have been compared with those in healthy, postmenopausal women. Exemestane appeared to be more rapidly absorbed in the women with breast cancer than in the healthy women, with a mean tmax of 1.2 hours in the women with breast cancer and 2.9 hours in the healthy women. After repeated dosing, the average oral clearance in women with advanced breast cancer was 45% lower than the oral clearance in healthy postmenopausal women, with corresponding higher systemic exposure. Mean AUC values following repeated doses in women with breast cancer (75.4 ng∙h/mL) were about twice those in healthy women (41.4 ng∙h/mL).
Absorption
Following oral administration of radiolabeled exemestane, at least 42% of radioactivity was absorbed from the gastrointestinal tract. Exemestane plasma levels increased by approximately 40% after a high-fat breakfast.
Distribution
Exemestane is distributed extensively into tissues. Exemestane is 90% bound to plasma proteins and the fraction bound is independent of the total concentration. Albumin and α1-acid glycoprotein both contribute to the binding. The distribution of exemestane and its metabolites into blood cells is negligible.
Metabolism and Excretion
Following administration of radiolabeled exemestane to healthy postmenopausal women, the cumulative amounts of radioactivity excreted in urine and feces were similar (42 ± 3% in urine and 42 ± 6% in feces over a 1-week collection period). The amount of drug excreted unchanged in urine was less than 1% of the dose. Exemestane is extensively metabolized, with levels of the unchanged drug in plasma accounting for less than 10% of the total radioactivity. The initial steps in the metabolism of exemestane are oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. Each metabolite accounts only for a limited amount of drug-related material. The metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug. One metabolite may have androgenic activity (see Pharmacodynamics, Other Endocrine Effects). Studies using human liver preparations indicate that cytochrome P-450 3A4 (CYP 3A4) is the principal isoenzyme involved in the oxidation of exemestane.
Special Populations
Geriatric
Healthy postmenopausal women aged 43 to 68 years were studied in the pharmacokinetic trials. Age-related alterations in exemestane pharmacokinetics were not seen over this age range.
Gender
The pharmacokinetics of exemestane following administration of a single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean age 55 years).
Race
The influence of race on exemestane pharmacokinetics has not been evaluated.
Hepatic Insufficiency
The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers (see PRECAUTIONS).
Renal Insufficiency
The AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers (see PRECAUTIONS).
Pediatric
The pharmacokinetics of exemestane have not been studied in pediatric patients.
Drug-Drug Interactions
Exemestane is metabolized by cytochrome P-450 3A4 (CYP 3A4) and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4. In a clinical pharmacokinetic study, ketoconazole showed no significant influence on the pharmacokinetics of exemestane. Although no other formal drug-drug interaction studies have been conducted, significant effects on exemestane clearance by CYP isoenzymes inhibitors appear unlikely. In a pharmacokinetic interaction study of 10 healthy postmenopausal volunteers pretreated with potent CYP 3A4 inducer rifampicin 600 mg daily for 14 days followed by a single dose of exemestane 25 mg, the mean plasma Cmax and AUC 0–∞ of exemestane were decreased by 41% and 54%, respectively (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Pharmacodynamics
Effect on Estrogens
Multiple doses of exemestane ranging from 0.5 to 600 mg/day were administered to postmenopausal women with advanced breast cancer. Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85% to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body aromatization (as measured by injecting radiolabeled androstenedione) by 98% in postmenopausal women with breast cancer. After a single dose of exemestane 25 mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after dosing and persisted for 4 to 5 days.
Effect on Corticosteroids
In multiple-dose trials of doses up to 200 mg daily, exemestane selectivity was assessed by examining its effect on adrenal steroids. Exemestane did not affect cortisol or aldosterone secretion at baseline or in response to ACTH at any dose. Thus, no glucocorticoid or mineralocorticoid replacement therapy is necessary with exemestane treatment.
Other Endocrine Effects
Exemestane does not bind significantly to steroidal receptors, except for a slight affinity for the androgen receptor (0.28% relative to dihydrotestosterone). The binding affinity of its 17-dihydrometabolite for the androgen receptor, however, is 100-times that of the parent compound. Daily doses of exemestane up to 25 mg had no significant effect on circulating levels of androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxyprogesterone, and were associated with small decreases in circulating levels of testosterone. Increases in testosterone and androstenedione levels have been observed at daily doses of 200 mg or more. A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with daily exemestane doses of 2.5 mg or higher. Slight, nondose-dependent increases in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed even at low doses as a consequence of feedback at the pituitary level. Exemestane 25 mg daily had no significant effect on thyroid function [free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH)].
Coagulation and Lipid Effects
In study 027 of postmenopausal women with early breast cancer treated with exemestane (N=73) or placebo (N=73), there was no change in the coagulation parameters activated partial thromboplastin time [APTT], prothrombin time [PT] and fibrinogen. Plasma HDL cholesterol was decreased 6–9% in exemestane treated patients; total cholesterol, LDL cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B, and lipoprotein-a were unchanged. An 18% increase in homocysteine levels was also observed in exemestane treated patients compared with a 12% increase seen with placebo.
CLINICAL STUDIES
Adjuvant Treatment in Early Breast Cancer
The Intergroup Exemestane Study 031 (IES) was a randomized, double-blind, multicenter, multinational study comparing exemestane (25 mg/day) versus tamoxifen (20 or 30 mg/day) in postmenopausal women with early breast cancer. Patients who remained disease-free after receiving adjuvant tamoxifen therapy for 2 to 3 years were randomized to receive 3 to 2 years of AROMASIN or tamoxifen to complete a total of 5 years of hormonal therapy.
The primary objective of the study was to determine whether, in terms of disease-free survival, it was more effective to switch to AROMASIN rather than continuing tamoxifen therapy for the remainder of five years. Disease-free survival was defined as the time from randomization to time of local or distant recurrence of breast cancer, contralateral invasive breast cancer, or death from any cause.
The secondary objectives were to compare the two regimens in terms of overall survival and long-term tolerability. Time to contralateral invasive breast cancer and distant recurrence-free survival were also evaluated.
A total of 4724 patients in the intent-to-treat (ITT) analysis were randomized to AROMASIN (exemestane tablets) 25 mg once daily (N = 2352) or to continue to receive tamoxifen once daily at the same dose received before randomization (N = 2372). Demographics and baseline tumor characteristics are presented in Table 1. Prior breast cancer therapy is summarized in Table 2.
Table 1. Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Parameter Exemestane
(N = 2352) Tamoxifen
(N = 2372)
*
Results for receptor status include the results of the post-randomization testing of specimens from subjects for whom receptor status was unknown at randomization.
†
Only one subject in the exemestane group had unknown ER status and positive PgR status.
Age (years):
Median age (range) 63.0 (38.0 – 96.0) 63.0 (31.0 – 90.0)
Race, n (%):
Caucasian 2315 (98.4) 2333 (98.4)
Hispanic 13 (0.6) 13 (0.5)
Asian 10 (0.4) 9 (0.4)
Black 7 (0.3) 10 (0.4)
Other/not reported 7 (0.3) 7 (0.3)
Nodal status, n (%):
Negative 1217 (51.7) 1228 (51.8)
Positive 1051 (44.7) 1044 (44.0)
1–3 Positive nodes 721 (30.7) 708 (29.8)
4–9 Positive nodes 239 (10.2) 244 (10.3)
9 Positive nodes 88 (3.7) 86 (3.6)
Not reported 3 (0.1) 6 (0.3)
Unknown or missing 84 (3.6) 100 (4.2)
Histologic type, n (%):
Infiltrating ductal 1777 (75.6) 1830 (77.2)
Infiltrating lobular 341 (14.5) 321 (13.5)
Other 231 (9.8) 213 (9.0)
Unknown or missing 3 (0.1) 8 (0.3)
Receptor status*, n (%):
ER and PgR Positive 1331 (56.6) 1319 (55.6)
ER Positive and PgR Negative/Unknown 677 (28.8) 692 (29.2)
ER Unknown and PgR Positive†/Unknown 288 (12.2) 291 (12.3)
ER Negative and PgR Positive 6 (0.3) 7 (0.3)
ER Negative and PgR Negative/Unknown (none positive) 48 (2.0) 58 (2.4)
Missing 2 (0.1) 5 (0.2)
Tumor Size, n (%):
≤ 0.5 cm 58 (2.5) 46 (1.9)
0.5 – 1.0 cm 315 (13.4) 302 (12.7)
1.0 – 2 cm 1031 (43.8) 1033 (43.5)
2.0 – 5.0 cm 833 (35.4) 883 (37.2)
5.0 cm 62 (2.6) 59 (2.5)
Not reported 53 (2.3) 49 (2.1)
Tumor Grade, n (%):
G1 397 (16.9) 393 (16.6)
G2 977 (41.5) 1007 (42.5)
G3 454 (19.3) 428 (18.0)
G4 23 (1.0) 19 (0.8)
Unknown/Not Assessed/Not reported 501 (21.3) 525 (22.1)
Table 2. Prior Breast Cancer Therapy of Patients in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Parameter Exemestane
(N = 2352) Tamoxifen
(N = 2372)
*
The 30 mg dose was used only in Denmark, where this dose was the standard of care.
Type of surgery, n (%):
Mastectomy 1232 (52.4) 1242 (52.4)
Breast-conserving 1116 (47.4) 1123 (47.3)
Unknown or missing 4 (0.2) 7 (0.3)
Radiotherapy to the breast, n (%):
Yes 1524 (64.8) 1523 (64.2)
No 824 (35.5) 843 (35.5)
Not reported 4 (0.2) 6 (0.3)
Prior therapy, n (%):
Chemotherapy 774 (32.9) 769 (32.4)
Hormone replacement therapy 567 (24.1) 561 (23.7)
Bisphosphonates 43 (1.8) 34 (1.4)
Duration of tamoxifen therapy at randomization (months):
Median (range) 28.5 (15.8 – 52.2) 28.4 (15.6 – 63.0)
Tamoxifen dose, n (%):
20 mg 2270 (96.5) 2287 (96.4)
30 mg* 78 (3.3) 75 (3.2)
Not reported 4 (0.2) 10 (0.4)
After a median duration of therapy of 27 months and with a median follow-up of 34.5 months, 520 events were reported, 213 in the AROMASIN group and 307 in the tamoxifen group (Table 3).
Table 3. Primary Endpoint Events (ITT Population)
Event First Events
N (%)
Exemestane
(N = 2352) Tamoxifen
(N = 2372)
Loco-regional recurrence 34 (1.45) 45 (1.90)
Distant recurrence 126 (5.36) 183 (7.72)
Second primary – contralateral breast cancer 7 (0.30) 25 (1.05)
Death – breast cancer 1 (0.04) 6 (0.25)
Death – other reason 41 (1.74) 43 (1.81)
Death – missing/unknown 3 (0.13) 5 (0.21)
Ipsilateral breast cancer 1 (0.04) 0
Total number of events 213 (9.06) 307 (12.94)
Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.69, 95% CI: 0.58, 0.82, P = 0.00003, Table 4, Figure 1] in the AROMASIN arm compared to the tamoxifen arm. In the hormone receptor-positive subpopulation representing about 85% of the trial patients, disease-free survival was also statistically significantly improved (HR = 0.65, 95% CI: 0.53, 0.79, P = 0.00001) in the AROMASIN arm compared to the tamoxifen arm. Consistent results were observed in the subgroups of patients with node negative or positive disease, and patients who had or had not received prior chemotherapy. Overall survival was not significantly different in the two groups, with 116 deaths occurring in the AROMASIN group and 137 in the tamoxifen group.
Table 4. Efficacy Results from the IES Study in Postmenopausal Women with Early Breast Cancer
ITT Population Hazard Ratio
(95% CI) p-value
(log-rank test)
Disease free survival 0.69 (0.58–0.82) 0.00003
Time to contralateral breast cancer 0.32 (0.15–0.72) 0.00340
Distant recurrence free survival 0.74 (0.62–0.90) 0.00207
Overall survival 0.86 (0.67–1.10) 0.22962
ER and/or PgR positive
Disease free survival 0.65 (0.53–0.79) 0.00001
Time to contralateral breast cancer 0.22 (0.08–0.57) 0.00069
Distant recurrence free survival 0.73 (0.59–0.90) 0.00367
Overall survival 0.88 (0.67–1.17) 0.37460
Figure 1. Disease Free Survival in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Image from Drug Label Content
Treatment of Advanced Breast Cancer
Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.
The primary purpose of the three studies was evaluation of objective response rate (complete response [CR] and partial response [PR]). Time to tumor progression and overall survival were also assessed in the comparative trial. Response rates were assessed based on World Health Organization (WHO) criteria, and in the comparative study, were submitted to an external review committee that was blinded to patient treatment. In the comparative study, 769 patients were randomized to receive AROMASIN (exemestane tablets) 25 mg once daily (N = 366) or megestrol acetate 40 mg four times daily (N = 403). Demographics and baseline characteristics are presented in Table 5.
Table 5. Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Parameter AROMASIN
(N = 366) Megestrol Acetate
(N = 403)
Median Age (range) 65 (35–89) 65 (30–91)
ECOG Performance Status
0 167 (46%) 187 (46%)
1 162 (44%) 172 (43%)
2 34 (9%) 42 (10%)
Receptor Status
ER and/or PgR + 246 (67%) 274 (68%)
ER and PgR unknown 116 (32%) 128 (32%)
Responders to prior tamoxifen 68 (19%) 85 (21%)
NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis
Visceral ± other sites 207 (57%) 239 (59%)
Bone only 61 (17%) 73 (18%)
Soft tissue only 54 (15%) 51 (13%)
Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen Therapy
Adjuvant or Neoadjuvanty 145 (40%) 152 (38%)
Advanced Disease, Outcome
CR, PR or SD≥ 6 months 179 (49%) 210 (52%)
SD< 6 months, PD or NE 42 (12%) 41 (10%)
Prior Chemotherapy
For advanced disease ± adjuvant 58 (16%) 67 (17%)
Adjuvant only 104 (28%) 108 (27%)
No chemotherapy 203 (56%) 226 (56%)
The efficacy results from the comparative study are shown in Table 6. The objective response rates observed in the two treatment arms showed that AROMASIN was not different from megestrol acetate. Response rates for AROMASIN from the two single-arm trials were 23.4% and 28.1%.
Table 6. Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Response Characteristics AROMASIN
(N=366) Megestrol Acetate
(N=403)
Abbreviations: CR = complete response, PR = partial response, SD = stable disease (no change), TTP = time to tumor progression, C.I. = confidence interval, MA = megestrol acetate, AR = AROMASIN
Objective Response Rate = CR + PR (%) 15.0 12.4
Difference in Response Rate (AR-MA) 2.6
95% C. I. 7.5, -2.3
CR (%) 2.2 1.2
PR (%) 12.8 11.2
SD ≥ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
Hazard Ratio (AR-MA) 0.84
There were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. The Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 2.
Figure 2. Time to Tumor Progression in the Comparative Study of Postmenopausal Women With Advanced Breast Cancer Whose Disease Had Progressed After Tamoxifen Therapy
The difference here is the test above was on postmenopausal women vs males in the other test
From the 2 test we can see that half life differs in men (8.9h) vs women (24H) but according to hookerscience these test don't mean anything.
Based on the fact that exemestane has a 8.9h half life in males indicates that administering twice a daily makes the most sense for men who want to yield the ultimate results.
I hope everyone takes the time to read what is below. This is the kind of individuals giving out information on this board. It's called the blind leading the blind. Someone saying a medical study on this topic has no merit shows complete ignorance. I feel bad for the people who take recommendations from this guy.
Because Aromasin is a steroidal aromatase inhibitor – a characteristic that neither of the two other major aromatase inhibitors possesses – it does exhibit androgenic activity in the body as evidenced by various studies as well as anecdotal reports by anabolic steroid users. This might even be a beneficial effect for individuals looking to use Aromasin during PCT, which is a period where aggression and drive is often times at an all-time low. As noted by two studies, Arimidex and Letrozole have no androgenic, progestrogenic, or estrogenic effects (such as weight gain, acne, or hypertrichosis), but Aromasin exhibits weak androgenic properties, and its use at higher doses has been associated with steroidal-like side effects such as minor lean mass gain and acne[3] [4]. These effects are normally seen with Aromasin doses of 25mg or higher.
In addition, Aromasin’s metabolite 17-hydroexemestane is a much more potent androgen as well, and also serves to further enhance the androgenic effects of aromasin[5]. It must be understood that Aromasin’s androgenic effect is very minimal at best, but might still present itself in minor levels (tiny bouts of acne, etc.) although individuals that are very sensitive to androgenic side effects should be aware of this. Normally the androgenic effects resultant of Aromasin side effects should not be an issue.
Androgenic side effects can include: increased sebum secretion (oily skin), increased bouts of acne (linked to increased sebum secretion), bodily and facial hair growth, benign prostatic hypertrophy (BPH), and the increased risk of triggering Male Pattern Baldness (MPB) in individuals that possess the genetic trait required for the condition to manifest itself.
Junk based on what how the product looks? Now I understand why you and your buddy hooker are hanging around here because you both have the abilities to look at vials and determine the quality.
Not by the way it looks, although it didnt look very good. I was taking up to 6 mg a wk of a-dex and still had itchy nips, water weight and no aching joints, at 2 mg eod i shouldn't have had those problems. i switch sources and dropped dose considerably and problem solved. I contacted pp and let them know about situation and they did not handle it well
And What?? do you think they didn't use "pharmacy brand" in the medical study? Either way It doesn't change the fact the optimal dosage for estrogen suppression is 25 mg with a 9 hour half life. Hence why guys like myself and anyone else with common sense dose 2 x a day. Look you can be mr popular all you want it doesn't change the fact you don't know shit.
Pharmacy was used in the study. Purc peps is rat food. Noone here's running that much or even near that much on other peps brands and certainly not pharmacy brand.
You can POst any study you want but it's not translating into real HUMAN usage. And popularity is not common sence. Real world use and seeing given advice work daily is proof.
So let me get this straight? You are saying leave it to bioscience aka hookerscience rather then believe the medical community and tests they've ran on the product? You are a special kind of stupid aren't you.
I will assure you people who have a clue pro's and top national level competitors run 25 or 12.5 mg 2x a day. This place is ran by Jack asses like you giving out misinformation. Why do you think the pills are 25mg so people can break them into 4ths? No because that's the dose. You are honestly one of if not the stupidest people here. The sad thing is kids listen to you and they have no clue you're a dumb ass because you have some numbers by your name. Keep giving out misinformation and saying medical reports have no value. It shows how ignorant you are.
I would like for you to explain to me how a middle aged man running 2g of test a week could keep is E in check with 6.25g of exemestane a day. Ready go real life scenario man.
I'm confused about what you are running...
is it 2000mg a week of test and 50mg a day of aromasin?
If this is a troll promoting PP, I'm getting the impression that the aromasin is weak as hell. It shouldn't take 50mg a day to knock down the estro from 7,000 serum of test.
I may be a noob, but I can see that your 1/4 strength aromasin is perfectly matched to your 1/2 strength gear.
Your bloods are good to go, so enjoy your cycle.
Something isn't right... Test levels should be higher running 2g. What else are you running?
How many times a week are you pinning and how many days post inject were bloods taken?
StevebPP is still good shit
Phhh boy....... I just don't know these days!!
Don't know what?
What's your baseline estro and test?
These numbers were during and after a toremifene and clomiphene pct
sept 2013 test level 71 E 24
Oct 2013 test level 60 E < 5
Dec 2013 test level 76 E 15
With GnRH, HCG 500 mg EOD and Clomiphene 50 mg ed. I think I was able to get my test level up to the mid 200s but that report is on my desk at work.
damn -33 karma no buneo
I don't care about a popularity contest. I graduated from HS over 20 years ago. I am here to let the community know people like hooker don't know shit. Him and his little gang can neg me all they want.
RustyhookerI didnt neg you. Just pay your bill for your PP shop. Put out good products.
6 thumbs down wouldn't pop a troll tag. You messed up by being a shill.
Do you honestly think I care about about a number by my name? What a joke.
RustyhookerYour number and name fit nicely.
Did I hear right you plan on competing soon? Lol
JHhow about this study stating the 24 hr terminal half life and the 25mg optimal dosage?
Metabolism and Excretion
Following administration of radiolabeled exemestane to healthy postmenopausal women, the cumulative amounts of radioactivity excreted in urine and feces were similar (42 ± 3% in urine and 42 ± 6% in feces over a 1-week collection period). The amount of drug excreted unchanged in urine was less than 1% of the dose. Exemestane is extensively metabolized, with levels of the unchanged drug in plasma accounting for less than 10% of the total radioactivity. The initial steps in the metabolism of exemestane are oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. Each metabolite accounts only for a limited amount of drug-related material. The metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug. One metabolite may have androgenic activity (see Pharmacodynamics, Other Endocrine Effects). Studies using human liver preparations indicate that cytochrome P-450 3A4 (CYP 3A4) is the principal isoenzyme involved in the oxidation of exemestane.
Special Populations
Geriatric
Healthy postmenopausal women aged 43 to 68 years were studied in the pharmacokinetic trials. Age-related alterations in exemestane pharmacokinetics were not seen over this age range.
Gender
The pharmacokinetics of exemestane following administration of a single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean age 55 years).
Race
The influence of race on exemestane pharmacokinetics has not been evaluated.
Hepatic Insufficiency
The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers (see PRECAUTIONS).
Renal Insufficiency
The AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers (see PRECAUTIONS).
Pediatric
The pharmacokinetics of exemestane have not been studied in pediatric patients.
Drug-Drug Interactions
Exemestane is metabolized by cytochrome P-450 3A4 (CYP 3A4) and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4. In a clinical pharmacokinetic study, ketoconazole showed no significant influence on the pharmacokinetics of exemestane. Although no other formal drug-drug interaction studies have been conducted, significant effects on exemestane clearance by CYP isoenzymes inhibitors appear unlikely. In a pharmacokinetic interaction study of 10 healthy postmenopausal volunteers pretreated with potent CYP 3A4 inducer rifampicin 600 mg daily for 14 days followed by a single dose of exemestane 25 mg, the mean plasma Cmax and AUC 0–∞ of exemestane were decreased by 41% and 54%, respectively (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Pharmacodynamics
Effect on Estrogens
Multiple doses of exemestane ranging from 0.5 to 600 mg/day were administered to postmenopausal women with advanced breast cancer. Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85% to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body aromatization (as measured by injecting radiolabeled androstenedione) by 98% in postmenopausal women with breast cancer. After a single dose of exemestane 25 mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after dosing and persisted for 4 to 5 days.
Effect on Corticosteroids
In multiple-dose trials of doses up to 200 mg daily, exemestane selectivity was assessed by examining its effect on adrenal steroids. Exemestane did not affect cortisol or aldosterone secretion at baseline or in response to ACTH at any dose. Thus, no glucocorticoid or mineralocorticoid replacement therapy is necessary with exemestane treatment.
Other Endocrine Effects
Coagulation and Lipid Effects
In study 027 of postmenopausal women with early breast cancer treated with exemestane (N=73) or placebo (N=73), there was no change in the coagulation parameters activated partial thromboplastin time [APTT], prothrombin time [PT] and fibrinogen. Plasma HDL cholesterol was decreased 6–9% in exemestane treated patients; total cholesterol, LDL cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B, and lipoprotein-a were unchanged. An 18% increase in homocysteine levels was also observed in exemestane treated patients compared with a 12% increase seen with placebo.
CLINICAL STUDIES
Adjuvant Treatment in Early Breast Cancer
The Intergroup Exemestane Study 031 (IES) was a randomized, double-blind, multicenter, multinational study comparing exemestane (25 mg/day) versus tamoxifen (20 or 30 mg/day) in postmenopausal women with early breast cancer. Patients who remained disease-free after receiving adjuvant tamoxifen therapy for 2 to 3 years were randomized to receive 3 to 2 years of AROMASIN or tamoxifen to complete a total of 5 years of hormonal therapy.
The primary objective of the study was to determine whether, in terms of disease-free survival, it was more effective to switch to AROMASIN rather than continuing tamoxifen therapy for the remainder of five years. Disease-free survival was defined as the time from randomization to time of local or distant recurrence of breast cancer, contralateral invasive breast cancer, or death from any cause.
The secondary objectives were to compare the two regimens in terms of overall survival and long-term tolerability. Time to contralateral invasive breast cancer and distant recurrence-free survival were also evaluated.
A total of 4724 patients in the intent-to-treat (ITT) analysis were randomized to AROMASIN (exemestane tablets) 25 mg once daily (N = 2352) or to continue to receive tamoxifen once daily at the same dose received before randomization (N = 2372). Demographics and baseline tumor characteristics are presented in Table 1. Prior breast cancer therapy is summarized in Table 2.
Table 1. Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Parameter Exemestane
(N = 2352) Tamoxifen
(N = 2372)
*
Results for receptor status include the results of the post-randomization testing of specimens from subjects for whom receptor status was unknown at randomization.
†
Only one subject in the exemestane group had unknown ER status and positive PgR status.
Age (years):
Median age (range) 63.0 (38.0 – 96.0) 63.0 (31.0 – 90.0)
Race, n (%):
Caucasian 2315 (98.4) 2333 (98.4)
Hispanic 13 (0.6) 13 (0.5)
Asian 10 (0.4) 9 (0.4)
Black 7 (0.3) 10 (0.4)
Other/not reported 7 (0.3) 7 (0.3)
Nodal status, n (%):
Negative 1217 (51.7) 1228 (51.8)
Positive 1051 (44.7) 1044 (44.0)
1–3 Positive nodes 721 (30.7) 708 (29.8)
4–9 Positive nodes 239 (10.2) 244 (10.3)
Table 3. Primary Endpoint Events (ITT Population)
Event First Events
N (%)
Exemestane
(N = 2352) Tamoxifen
(N = 2372)
Loco-regional recurrence 34 (1.45) 45 (1.90)
Distant recurrence 126 (5.36) 183 (7.72)
Second primary – contralateral breast cancer 7 (0.30) 25 (1.05)
Death – breast cancer 1 (0.04) 6 (0.25)
Death – other reason 41 (1.74) 43 (1.81)
Death – missing/unknown 3 (0.13) 5 (0.21)
Ipsilateral breast cancer 1 (0.04) 0
Total number of events 213 (9.06) 307 (12.94)
Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.69, 95% CI: 0.58, 0.82, P = 0.00003, Table 4, Figure 1] in the AROMASIN arm compared to the tamoxifen arm. In the hormone receptor-positive subpopulation representing about 85% of the trial patients, disease-free survival was also statistically significantly improved (HR = 0.65, 95% CI: 0.53, 0.79, P = 0.00001) in the AROMASIN arm compared to the tamoxifen arm. Consistent results were observed in the subgroups of patients with node negative or positive disease, and patients who had or had not received prior chemotherapy. Overall survival was not significantly different in the two groups, with 116 deaths occurring in the AROMASIN group and 137 in the tamoxifen group.
Table 4. Efficacy Results from the IES Study in Postmenopausal Women with Early Breast Cancer
ITT Population Hazard Ratio
(95% CI) p-value
(log-rank test)
Disease free survival 0.69 (0.58–0.82) 0.00003
Time to contralateral breast cancer 0.32 (0.15–0.72) 0.00340
Distant recurrence free survival 0.74 (0.62–0.90) 0.00207
Overall survival 0.86 (0.67–1.10) 0.22962
ER and/or PgR positive
Disease free survival 0.65 (0.53–0.79) 0.00001
Time to contralateral breast cancer 0.22 (0.08–0.57) 0.00069
Distant recurrence free survival 0.73 (0.59–0.90) 0.00367
Overall survival 0.88 (0.67–1.17) 0.37460
Figure 1. Disease Free Survival in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)
Image from Drug Label Content
Treatment of Advanced Breast Cancer
Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.
The primary purpose of the three studies was evaluation of objective response rate (complete response [CR] and partial response [PR]). Time to tumor progression and overall survival were also assessed in the comparative trial. Response rates were assessed based on World Health Organization (WHO) criteria, and in the comparative study, were submitted to an external review committee that was blinded to patient treatment. In the comparative study, 769 patients were randomized to receive AROMASIN (exemestane tablets) 25 mg once daily (N = 366) or megestrol acetate 40 mg four times daily (N = 403). Demographics and baseline characteristics are presented in Table 5.
Table 5. Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Parameter AROMASIN
(N = 366) Megestrol Acetate
(N = 403)
Median Age (range) 65 (35–89) 65 (30–91)
ECOG Performance Status
0 167 (46%) 187 (46%)
1 162 (44%) 172 (43%)
2 34 (9%) 42 (10%)
Receptor Status
ER and/or PgR + 246 (67%) 274 (68%)
ER and PgR unknown 116 (32%) 128 (32%)
Responders to prior tamoxifen 68 (19%) 85 (21%)
NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis
Visceral ± other sites 207 (57%) 239 (59%)
Bone only 61 (17%) 73 (18%)
Soft tissue only 54 (15%) 51 (13%)
Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen Therapy
Adjuvant or Neoadjuvanty 145 (40%) 152 (38%)
Advanced Disease, Outcome
CR, PR or SD≥ 6 months 179 (49%) 210 (52%)
SD< 6 months, PD or NE 42 (12%) 41 (10%)
Prior Chemotherapy
For advanced disease ± adjuvant 58 (16%) 67 (17%)
Adjuvant only 104 (28%) 108 (27%)
No chemotherapy 203 (56%) 226 (56%)
The efficacy results from the comparative study are shown in Table 6. The objective response rates observed in the two treatment arms showed that AROMASIN was not different from megestrol acetate. Response rates for AROMASIN from the two single-arm trials were 23.4% and 28.1%.
Table 6. Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy
Response Characteristics AROMASIN
(N=366) Megestrol Acetate
(N=403)
Abbreviations: CR = complete response, PR = partial response, SD = stable disease (no change), TTP = time to tumor progression, C.I. = confidence interval, MA = megestrol acetate, AR = AROMASIN
Objective Response Rate = CR + PR (%) 15.0 12.4
Difference in Response Rate (AR-MA) 2.6
95% C. I. 7.5, -2.3
CR (%) 2.2 1.2
PR (%) 12.8 11.2
SD ≥ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
Hazard Ratio (AR-MA) 0.84
There were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. The Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 2.
Figure 2. Time to Tumor Progression in the Comparative Study of Postmenopausal Women With Advanced Breast Cancer Whose Disease Had Progressed After Tamoxifen Therapy
Image from Drug Label Content
The difference here is the test above was on postmenopausal women vs males in the other test
From the 2 test we can see that half life differs in men (8.9h) vs women (24H) but according to hookerscience these test don't mean anything.
Based on the fact that exemestane has a 8.9h half life in males indicates that administering twice a daily makes the most sense for men who want to yield the ultimate results.
RustyhookerEdumakated folks know it's a suicide inhibitor. It doesn't need full time duty.
Where's your source tag?
I dont know where you come up with this stuff but its becoming comical.
I hope everyone takes the time to read what is below. This is the kind of individuals giving out information on this board. It's called the blind leading the blind. Someone saying a medical study on this topic has no merit shows complete ignorance. I feel bad for the people who take recommendations from this guy.
Rustyhooker50Mg of aromasin? Time to get some pharma. You'd do better for sure!
I remember the origional PP brand before it was sold. Back 3yrs ago. 6.25 was plenty aro to battle down a big cycle.
keep learning Hooker and one day you maybe OK!
Because Aromasin is a steroidal aromatase inhibitor – a characteristic that neither of the two other major aromatase inhibitors possesses – it does exhibit androgenic activity in the body as evidenced by various studies as well as anecdotal reports by anabolic steroid users. This might even be a beneficial effect for individuals looking to use Aromasin during PCT, which is a period where aggression and drive is often times at an all-time low. As noted by two studies, Arimidex and Letrozole have no androgenic, progestrogenic, or estrogenic effects (such as weight gain, acne, or hypertrichosis), but Aromasin exhibits weak androgenic properties, and its use at higher doses has been associated with steroidal-like side effects such as minor lean mass gain and acne[3] [4]. These effects are normally seen with Aromasin doses of 25mg or higher.
In addition, Aromasin’s metabolite 17-hydroexemestane is a much more potent androgen as well, and also serves to further enhance the androgenic effects of aromasin[5]. It must be understood that Aromasin’s androgenic effect is very minimal at best, but might still present itself in minor levels (tiny bouts of acne, etc.) although individuals that are very sensitive to androgenic side effects should be aware of this. Normally the androgenic effects resultant of Aromasin side effects should not be an issue.
Androgenic side effects can include: increased sebum secretion (oily skin), increased bouts of acne (linked to increased sebum secretion), bodily and facial hair growth, benign prostatic hypertrophy (BPH), and the increased risk of triggering Male Pattern Baldness (MPB) in individuals that possess the genetic trait required for the condition to manifest itself.
Hooker at what dose does exemestane start showing androgenic effects and start raising testosterone levels?
PP is junk!!! I totally agree. I used them religiously for 2 years then they shit the bed. I
Junk based on what how the product looks? Now I understand why you and your buddy hooker are hanging around here because you both have the abilities to look at vials and determine the quality.
Not by the way it looks, although it didnt look very good. I was taking up to 6 mg a wk of a-dex and still had itchy nips, water weight and no aching joints, at 2 mg eod i shouldn't have had those problems. i switch sources and dropped dose considerably and problem solved. I contacted pp and let them know about situation and they did not handle it well
Who did you buy from?
PURCHASEPEPTIDES.COM!!!
RustyhookerIn the beginning they were amazing! Wish they kept up.
Dumb ass. 6.25mg is all relevant to your test dose. Not to mention for the second time read the article below.
You stating that pp was sold shows you are absolutely clueless. It's been the same own since day 1.
http://www.ncbi.nlm.nih.gov/m/pubmed/14671195/
RustyhookerYou're the owner of pp. so how bout producing some good peps?
I don't own shit. So that's your response? That's the best come back you have? So much for you 6.25 mg theory. Hookerscience!
RustyhookerMy answer....PHARMACY BRAND ARO. Common sence.
PP was strong back in the day.
And What?? do you think they didn't use "pharmacy brand" in the medical study? Either way It doesn't change the fact the optimal dosage for estrogen suppression is 25 mg with a 9 hour half life. Hence why guys like myself and anyone else with common sense dose 2 x a day. Look you can be mr popular all you want it doesn't change the fact you don't know shit.
RustyhookerPharmacy was used in the study. Purc peps is rat food. Noone here's running that much or even near that much on other peps brands and certainly not pharmacy brand.
You can POst any study you want but it's not translating into real HUMAN usage. And popularity is not common sence. Real world use and seeing given advice work daily is proof.
So let me get this straight? You are saying leave it to bioscience aka hookerscience rather then believe the medical community and tests they've ran on the product? You are a special kind of stupid aren't you.
I will assure you people who have a clue pro's and top national level competitors run 25 or 12.5 mg 2x a day. This place is ran by Jack asses like you giving out misinformation. Why do you think the pills are 25mg so people can break them into 4ths? No because that's the dose. You are honestly one of if not the stupidest people here. The sad thing is kids listen to you and they have no clue you're a dumb ass because you have some numbers by your name. Keep giving out misinformation and saying medical reports have no value. It shows how ignorant you are.
I would like for you to explain to me how a middle aged man running 2g of test a week could keep is E in check with 6.25g of exemestane a day. Ready go real life scenario man.
No Stats No advice
Not looking for advice. If I want advice this is the last place I'll come.
I'm confused about what you are running...
is it 2000mg a week of test and 50mg a day of aromasin?
If this is a troll promoting PP, I'm getting the impression that the aromasin is weak as hell. It shouldn't take 50mg a day to knock down the estro from 7,000 serum of test.
Everyone here is a know it all and most don't know shit including you. Read on know it all.
Now I get it you did your first cycle last year so you must know it all.
http://www.ncbi.nlm.nih.gov/m/pubmed/14671195/
I may be a noob, but I can see that your 1/4 strength aromasin is perfectly matched to your 1/2 strength gear.
Your bloods are good to go, so enjoy your cycle.
great numbers. Where the test from big homie? Thats good shit i need right there. Am i missing something why did this get negged? +1
Nothing more then haters. Which is fine the blood work doesn't lie.
shoxingbiceps17He's a troll. He works for Purchase Peptides
The proof is in the blood work not the haters.
oh see im not in the loop. If thats the case -1
Something isn't right... Test levels should be higher running 2g. What else are you running?
How many times a week are you pinning and how many days post inject were bloods taken?
My bloods are fine Iam 4 weeks into my cycle. Those levels will rise in time.
Maybe another 5%? Even then it's still low.
Keep an eye out for next month BW.