Human Growth Hormone - Nutropin
Part 3
Nutropin® [somatropin (rDNA origin) for injection] is a human growth hormone (hGH) produced by recombinant DNA technology. Nutropin has 191 amino acid residues and a molecular weight of 22,125 daltons. The amino acid sequence of the product is identical to that of pituitary-derived human growth hormone. The protein is synthesized by a specific laboratory strain of E. coli as a precursor consisting of the rhGH molecule preceded by the secretion signal from an E. coli protein. This precursor is directed to the plasma membrane of the cell. The signal sequence is removed and the native protein is secreted into the periplasm so that the protein is folded appropriately as it is synthesized.
Nutropin is a highly purified preparation. Biological potency is determined by measuring the increase in body weight induced in hypophysectomized rats.
Nutropin is a sterile, white, lyophilized powder intended for subcutaneous administration after reconstitution with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). The reconstituted product is nearly isotonic at a concentration of 5 mg/mL growth hormone (GH) and has a pH of approximately 7.4.
Each 5 mg Nutropin vial contains 5 mg (approximately 15 IU) somatropin, lyophilized with 45 mg mannitol, 1.7 mg sodium phosphates (0.4 mg sodium phosphate monobasic and 1.3 mg sodium phosphate dibasic), and 1.7 mg glycine.
Each 10 mg Nutropin vial contains 10 mg (approximately 30 IU) somatropin, lyophilized with 90 mg mannitol, 3.4 mg sodium phosphates (0.8 mg sodium phosphate monobasic and 2.6 mg sodium phosphate dibasic), and 3.4 mg glycine.
Bacteriostatic Water for Injection, USP is sterile water containing 0.9 percent benzyl alcohol per mL as an antimicrobial preservative packaged in a multidose vial. The diluent pH is 4.5-7.0.
CLINICAL PHARMACOLOGY
General
In vitro and in vivo preclinical and clinical testing have demonstrated that Nutropin® [somatropin (rDNA origin) for injection] is therapeutically equivalent to pituitary-derived human GH (hGH). Pediatric patients who lack adequate endogenous GH secretion, patients with chronic renal insufficiency, and patients with Turner syndrome that were treated with Nutropin resulted in an increase in growth rate and an increase in insulin-like growth factor-I (IGF-I) levels similar to that seen with pituitary-derived hGH.
Actions that have been demonstrated for Nutropin, somatrem, and/or pituitary-derived hGH include:
A. Tissue Growth – 1) Skeletal Growth: GH stimulates skeletal growth in pediatric patients with growth failure due to a lack of adequate secretion of endogenous GH or secondary to chronic renal insufficiency and in patients with Turner syndrome. Skeletal growth is accomplished at the epiphyseal plates at the ends of a growing bone. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and one of its mediators, IGF-I. Serum levels of IGF-I are low in children and adolescents who are GH deficient, but increase during treatment with GH. In pediatric patients, new bone is formed at the epiphyses in response to GH and IGF-I. This results in linear growth until these growth plates fuse at the end of puberty. 2) Cell Growth: Treatment with hGH results in an increase in both the number and the size of skeletal muscle cells. 3) Organ Growth: GH influences the size of internal organs, including kidneys, and increases red cell mass. Treatment of hypophysectomized or genetic dwarf rats with GH results in organ growth that is proportional to the overall body growth. In normal rats subjected to nephrectomy-induced uremia, GH promoted skeletal and body growth.
B. Protein Metabolism – Linear growth is facilitated in part by GH-stimulated protein synthesis. This is reflected by nitrogen retention as demonstrated by a decline in urinary nitrogen excretion and blood urea nitrogen during GH therapy.
C. Carbohydrate Metabolism – GH is a modulator of carbohydrate metabolism. For example, patients with inadequate secretion of GH sometimes experience fasting hypoglycemia that is improved by treatment with GH. GH therapy may decrease insulin sensitivity. Untreated patients with chronic renal insufficiency and Turner syndrome have an increased incidence of glucose intolerance. Administration of hGH to adults or children resulted in increases in serum fasting and postprandial insulin levels, more commonly in overweight or obese individuals. In addition, mean fasting and postprandial glucose and hemoglobin A1c levels remained in the normal range.
D. Lipid Metabolism – In GH-deficient patients, administration of GH resulted in lipid mobilization, reduction in body fat stores, increased plasma fatty acids, and decreased plasma cholesterol levels.
E. Mineral Metabolism – The retention of total body potassium in response to GH administration apparently results from cellular growth. Serum levels of inorganic phosphorus may increase slightly in patients with inadequate secretion of endogenous GH, chronic renal insufficiency, or patients with Turner syndrome during GH therapy due to metabolic activity associated with bone growth as well as increased tubular reabsorption of phosphate by the kidney. Serum calcium is not significantly altered in these patients. Sodium retention also occurs. Adults with childhood-onset GH deficiency show low bone mineral density (BMD). (See PRECAUTIONS: Laboratory Tests.)
F. Connective Tissue Metabolism – GH stimulates the synthesis of chondroitin sulfate and collagen as well as the urinary excretion of hydroxyproline.
Pharmacokinetics
Subcutaneous Absorption – The absolute bioavailability of recombinant human growth hormone (rhGH) after subcutaneous administration in healthy adult males has been determined to be 81±20%. The mean terminal t1/2 after subcutaneous administration is significantly longer than that seen after intravenous administration (2.1±0.43 hr vs. 19.5±3.1 min) indicating that the subcutaneous absorption of the compound is slow and rate-limiting.
Distribution – Animal studies with rhGH showed that GH localizes to highly perfused organs, particularly the liver and kidney. The volume of distribution at steady state for rhGH in healthy adult males is about 50 mL/kg body weight, approximating the serum volume.
Metabolism – Both the liver and kidney have been shown to be important metabolizing organs for GH. Animal studies suggest that the kidney is the dominant organ of clearance. GH is filtered at the glomerulus and reabsorbed in the proximal tubules. It is then cleaved within renal cells into its constituent amino acids, which return to the systemic circulation.
Elimination – The mean terminal t1/2 after intravenous administration of rhGH in healthy adult males is estimated to be 19.5±3.1 minutes. Clearance of rhGH after intravenous administration in healthy adults and children is reported to be in the range of 116-174 mL/hr/kg.
Bioequivalence of Formulations – Nutropin has been determined to be bioequivalent to Nutropin AQ® [somatropin (rDNA origin) injection] based on the statistical evaluation of AUC and Cmax.
WARNINGS
Benzyl alcohol as a preservative in Bacteriostatic Water for Injection, USP has been associated with toxicity in newborns. When administering Nutropin® [somatropin (rDNA origin) for injection] to newborns, reconstitute with Sterile Water for Injection, USP. USE ONLY ONE DOSE PER NUTROPIN VIAL AND DISCARD THE UNUSED PORTION.
Because Nutropin may reduce insulin sensitivity, patients should be monitored for evidence of glucose intolerance.
Nutropin therapy in adults with GHD of adult onset was associated with an increase of median fasting insulin in the Nutropin 0.0125 mg/kg/day group from 9.0 µU/mL at baseline to 13.0 µU/mL at month 12 with a return to the baseline median after a 3-week post-washout period off GH therapy. In the placebo group there was no change from 8.0 µU/mL at baseline to month 12, and after the post-washout the median was 9.0 µU/mL. The between-treatment-groups difference in change from baseline to month 12 was significant, p In subjects with adult-onset GHD there was no between-treatment-group difference in changes from baseline to month 12 in mean HbA1c, p=0.08. In childhood-onset mean HbA1c increased in the Nutropin 0.025 mg/kg/day group from 5.2% at baseline to 5.5% at month 12, and did not change in the Nutropin 0.0125 mg/kg/day group from 5.1% at baseline or in the placebo group from 5.3% at baseline. The between-treatment-groups difference was significant, p=0.009.
ADVERSE REACTIONS
As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. GH antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. In clinical studies of pediatric patients that were treated with Nutropin® [somatropin (rDNA origin) for injection] for the first time, 0/107 growth hormone-deficient (GHD) patients, 0/125 CRI patients, and 0/112 Turner syndrome patients screened for antibody production developed antibodies with binding capacities 2 mg/L at six months.
In addition to an evaluation of compliance with the prescribed treatment program and thyroid status, testing for antibodies to GH should be carried out in any patient who fails to respond to therapy.
In studies in patients treated with Nutropin, injection site pain was reported infrequently.
Leukemia has been reported in a small number of GHD patients treated with GH. It is uncertain whether this increased risk is related to the pathology of GH deficiency itself, GH therapy, or other associated treatments such as radiation therapy for intracranial tumors. On the basis of current evidence, experts cannot conclude that GH therapy is responsible for these occurrences. The risk to GHD, CRI, or Turner syndrome patients, if any, remains to be established.
Other adverse drug reactions that have been reported in GH–treated patients include the following: 1) Metabolic: Mild, transient peripheral edema. In GHD adults, edema or peripheral edema was reported in 41% of GH-treated patients and 25% of placebo-treated patients. 2) Musculoskeletal: Arthralgias; carpal tunnel syndrome. In GHD adults, arthralgias and other joint disorders were reported in 27% of GH-treated patients and 15% of placebo-treated patients. 3) Skin: Rare increased growth of pre-existing nevi; patients should be monitored for malignant transformation. 4) Endocrine: Gynecomastia. Rare pancreatitis.
OVERDOSAGE
Acute overdosage could lead to hyperglycemia. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess GH. (See recommended and maximal dosage instructions given below.)
PREPARATIONS
To prepare the Nutropin solution, inject the Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) into the Nutropin vial, aiming the stream of liquid against the glass wall. Then swirl the product vial with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE. Because Nutropin is a protein, shaking can result in a cloudy solution. The Nutropin solution should be clear immediately after reconstitution. Occasionally, after refrigeration, you may notice that small colorless particles of protein are present in the Nutropin solution. This is not unusual for solutions containing proteins. If the solution is cloudy immediately after reconstitution or refrigeration, the contents MUST NOT be injected.
Before needle insertion, wipe the septum of both the Nutropin and diluent vials with rubbing alcohol or an antiseptic solution to prevent contamination of the contents by microorganisms that may be introduced by repeated needle insertions. It is recommended that Nutropin be administered using sterile, disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be drawn from the vial with reasonable accuracy.
STABILITY AND STORAGE
Before Reconstitution–Nutropin® [somatropin (rDNA origin) for injection] and Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) must be stored at 2°C-8°C/36°F-46°F (under refrigeration). Avoid freezing the vials of Nutropin and Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). Expiration dates are stated on the labels.
After Reconstitution–Vial contents are stable for 14 days when reconstituted with Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) and stored at 2°C-8°C/36°F-46°F (under refrigeration). Store the unused portion of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved) at 2°C-8°C/36°F-46°F (under refrigeration). Avoid freezing the reconstituted vial of Nutropin and the Bacteriostatic Water for Injection, USP (benzyl alcohol preserved).
HOW SUPPLIED
Nutropin® [somatropin (rDNA origin) for injection] is supplied as 5 mg (approximately 15 IU) or 10 mg (approximately 30 IU) of lyophilized, sterile somatropin per vial.
Each 5 mg carton contains two vials of Nutropin® [somatropin (rDNA origin) for injection] (5 mg per vial) and one 10 mL multiple dose vial of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). NDC 50242-072-02
Each 10 mg carton contains two vials of Nutropin® [somatropin (rDNA origin) for injection] (10 mg per vial) and two 10 mL multiple dose vials of Bacteriostatic Water for Injection, USP (benzyl alcohol preserved). NDC 50242-018-20
HGH for Bodybuilding Use
Bodybuilders that have entertained the administration of the somatropin versions of GH which had contained the 191 amino acid chain, as this allegedly been more effective than its contender of 192 amino acids, Protropin. Since Human Growth Hormone is a master hormone, exogenous administration had acted as a messenger which had ultimately resulted in the endocrine system having returned the natural biological harmony.
Synthetic Growth Hormone had a strong anabolic effect that had caused an increased protein synthesis which had led to an increase, and an enlargement of the muscle cells. The ability of muscular hyperplasia, had made the synthetic Growth Hormone unique, as this property had been unattainable by steroidal compound intake alone. The administration of synthetic Growth Hormone had also strengthened the connective tissues, tendons, cartilages that had often been responsible for strength increases, which had prevented potential injuries.
Consequently, several bodybuilders had claimed that the exclusive use of synthetic Growth Hormone although anabolic, had very little anti-catabolic activity, and had not produced any beneficial gains by itself. However, the addition of anabolic steroids (characteristic of preventing catabolism), had produced a tremendous degree of synergism, which inevitably had often promoted a very much desired, significant increase in lean muscle tissue.
In fact, many bodybuilders had claimed that an injectable synthetic Growth Hormone, along with the required combination of Insulin and Cytomel (T3 Thyroid hormone) had not only allowed for the maximum anabolic effect, but also had enabled the liver to have produced and have released the maximum amounts of Somatomedin and IGF-1. IGF-1is the one that causes the various effects in the body. This effect had been however, somewhat restricted, as the liver had only been capable of having produced a limited amount of these substances.
Some bodybuilders also had frequently engaged in the administration of exogenous synthetic Growth Hormone, for the added desired entity of having burned bodyfat for energy, which distinguishably had often led to a pronounced fat reduction, even on a high calorie intake. In fact, if this compound had been utilized when calories had been restricted, the body had generally counteracted by having reduced the release of insulin and the T3 thyroid hormone. This in turn, had reduced the anabolic effect. Miraculously, many bodybuilders had also reported that a reasonable increase in proper calories had not resulted in the accumulation of fat. However, if this compound had been utilized by bodybuilders only for the lipolysis (fat loss) properties, then the thyroid hormone levels had also been required to have been increased during the synthetic Growth Hormone treatment. Most bodybuilders had generally easily accomplished this by having consumed a complete meal every 3 hours.
Consequently, many bodybuilders had claimed that the effects of Growth Hormone had not been adventageous (particularly when dieting), when they also had combined the anti-catabolic compound, Clenbuterol. This combination actually reduced the bodys own natural release of insulin and T3. On an average of 6 to 8 months, most bodybuilders had encountered an increase in lean muscle tissue of approximately 8.8% and a reduction of 14% bodyfat!
Unfortuneatly, several bodybuilders have been unsuccessful in having attempted the utilization of exogenous synthetic Growth Hormones, therefore, had often rendered this compounds efficacy worthless. Accordingly, there had generally been many probable reasons for these warranted accusations; which had argumentatively not supported these theories.
All of the current synthetic versions of Somatropin had been expensive, and as for the most part, severla self administering bodybuilders simply could not have afforded the required dosages which would have produced the desired results. Unless a possible cycle had been affordable or obtainable, most bodybuilders had not ventured to have wasted both money and effort in an amount that would have been insufficient to have produced a positive outcome. A full dosage taken regularly over an extended enough duration, had been necessary for this compound to be effective.
Other common problems which some bodybuilders had sometimes encountered had been that the body also had required more thyroid hormones, insulin, corticosteroids, gonadotropins, Estrogen, androgens, and anabolics, in addition to the administration of synthetic Growth Hormone. If these substances had been absent, or if the synthetic Growth Hormone had been singularly taken, it had usually resulted in considerably lessened effects, if any had been experienced at all. Therefore, if bodybuilders had also entertained the additional combination of steroidal compounds, thyroid hormones, and in particular, insulin, they had often been able to have had produced potential optimal anabolic results.
Bodybuilders Dosages and administration.
Many bodybuilders have claimed that the utilization of small regular dosages had seemed to be the most effective, as the administered synthetic Growth Hormone effect hasd been almost immediate due to the rapid increase of the serum concentration in the blood. The administration of synthetic Growth Hormone had also stimulated the liver which in turn, had produced and released somatomedins and insulin-like growth factors. This effect had generally transpired into desired results in the bodybuilders body. Consequently, since the liver had been only able to have produced a limited amount of these substances, and had reacted more favorably to smaller dosages, it had not proven to have been advantageous to have increased the administered injection, in further attempts to have acquired larger quantities of somatomedins and insulin-like growth factors.
Several bodybuilders had claimed that if the synthetic Growth Hormone had been administered subcutaneously (beneath the skin) at the same point of injection, for a repeated amoutn of times, a loss of fat tissue had been frequently experienced. Evidently, in order to have avoided lipoatrophy (localized fat tissue loss), many athletes had generally alternated the injection sites from one side of the body to the other. Commonly, daily subcutaneous injections had been preferred (when financially permitted) at dosages of 8 I.U.s a day. Top bodybuilders had claimed to have injected the synthetic form of Growth Hormone anywhere in the range of 4 to 16 IU's a day. Since this compound had a half-life time of less than one hour, many athletes had often furher divided their daily dose into 3 or 4 subcutaneous injections of 2 to 4 I.U.'s each. However, the effect of synthetic Growth Hormone had largly been dosage-dependant. Sometimes, a typical 200lb bodybuilder had administered approxiimately 5.5mg (or approximately 15 I.U.'s ) daily, which had been slightly more thatn the 5mg amount in the bottle. This dosage schedule is extremely expensive and not viable to most bodybuilders.
In our world, it is in the opinion of mine and some other "gurus" of the Underground to be able to take at least 2 I.U.'s a day. 4 I.U would be better, but if you dont have the money, then 2 is fine. Divide the dosage. If you are taking 4 I.U.'s a day, then subcutaneously inject 2 I.U.'s in the morning and the other 2 I.U.'s later on. ( preferably after a workout). In order for a HGH cycle to be effective, the cycle must last at least 6 weeks. Also, during your cycles, you need to take at least 2 days off to give your pituitary gland a break. So a week would count as 5 days on, 2 days off. This cycle is effective, and more affordable by the average bodybuilder. It is even more adventagious to make the cycle last 3 - 4 months.
As a bodybuilder like you, I am ready to start a regimine of HGH, Sustanon, Enanthate, Insulin, T3. My cycle will be something like this.
Week 1 - Week 8
3 IUs of HGH/day Monday - Friday (1.5 IU in the am -- 1.5IU after workouts or afternoon)
8 IU of Insulin Monday -Friday (4 I.U. in the am -- 4 I.U. after workouts or afternoon)
250mg of Sustanon / week
200mg of Enanthate/week
25mg of Halotestin/day (everyday)
50mcg of Cytomel/ day (25mcg in the am -- 25mcg in the afternoon) (everyday)
I might skip the Cytomel. That is a long time to be on Thyroid medication. I will report my progress in next months Newsletter.