Sermorelin Acetate

Sermorelin acetate (sermorelin) is the acetate salt of an amidated synthetic 29- amino acid peptide (GRF 1-29 NH 2 ) that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting of 44 amino acid residues. The structural formula for sermorelin acetate is:

The free base of sermorelin has the empirical formula C 149 H 246 N 44 O 42 S and a molecular weight of 3,358 daltons.

Sermorelin is a sterile, non-pyrogenic, lyophilized powder intended for subcutaneous injection after reconstitution with Sodium Chloride Injection, USP. The reconstituted solution has a pH of 5.0 to 5.5.

Sermorelin is available in vials. The quantitative composition per vial is:

0.5 mg vial: Each vial contains 0.5 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate and monobasic sodium phosphate buffer.
3.0 mg vial: Each vial contains 3.0 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate and monobasic sodium phosphate buffer.

Sermorelin is approved for diagnostic evaluation of pituitary function and also for increasing growth in children. Off label usage may include acute or age-related growth hormone insufficiency

A large proportion of patients develop anti- GRF antibodies at least once during treatment with Sermorelin. The significance of these antibodies is not clear and often a positive test at one growth assessment will become negative by the next assessment. The presence of antibodies does not appear to affect growth or appear to be related to a specific adverse reaction profile. No generalized allergic reactions to Sermorelin have been reported.

The most common treatment-related adverse event (occurring in about 1 patient in 6) is local injection reaction characterized by pain, swelling or redness. Of 350 patients exposed to Sermorelin in clinical trials, three discontinued therapy due to injection reactions. Other treatment-related adverse events had individual occurrence rates of less than 1% and include: headache, flushing, dysphagia, dizziness, hyperactivity, somnolence and urticaria.

When administered intravenously for diagnostic use, the following adverse reactions have been noted: flushing of the face, injection site pain, redness and/or swelling, nausea, headache, vomiting, dysgeusia, pallor and tightness in the chest.

Drug Abuse and Dependence

The clinical pharmacology suggests that Sermorelin is very unlikely to be associated with drug abuse or dependence and there have been no reports of this from clinical trials.

No information provided.

Sermorelin acetate for injection increases plasma growth hormone (GH) concentration by stimulating the pituitary gland to release GH. Sermorelin is similar to the native hormone (GRF [1-44]-NH 2 ) in its ability to stimulate GH secretion in humans. Pharmacokinetics

Absorption

In subcutaneous administration of 2 mg sermorelin to 12 normal volunteers, peak concentrations of sermorelin were reached in 5-20 minutes. The mean absolute bioavailability after SC administration is about 6%.

Distribution

After intravenous administration of 0.25-1.0 mg Sermorelin® to 12 normal volunteers, the mean volume of distribution ranged between 23.7-25.8 liters.

Metabolism

No metabolism studies have been performed in humans.

Elimination

Sermorelin is rapidly cleared from the circulation, with clearance values in adults ranging between 2.4-2.8 L/min. The halflife of Sermorelin is short, 11-12 minutes after either intravenous or subcutaneous administration.

Special Populations

Gender/Age: No gender data are available in pediatric patients. In normal adults, the clearance of sermorelin in men and women is similar. No age data are available.

Renal/Hepatic Insufficiency: No data are available.