Somatrem

Identification

Summary

Somatrem is a recombinant growth hormone used to treat adult growth hormone deficiency and treat disrupted growth in children due to growth hormone insufficiency or deficiency, turner's syndrome, chronic renal failure, and small stature for gestational age.

Generic Name

Somatrem

DrugBank Accession Number

DB09098

Background

Despite the ability of almost all contemporary recombinant growth hormones to cause definite and demonstrable increases in growth rate in patients who are administered the drug, the use of these agents continues to be mired in persistent bioethical debate ¹. Such discussion revolves around whether patients' natural disposition of short stature should be considered a medical condition justifying medical treatment with such hormone therapy - especially when these hormone agents have been proven effective at increasing the height of children with or without growth hormone deficiency ¹.

Type

Biotech

Groups

Approved, Investigational, Withdrawn

Biologic Classification

Protein Based Therapies
Other protein based therapies

Protein Structure

Protein Chemical Formula: C₉₉₅H₁₅₃₇N₂₆₃O₃₀₁S₈
Protein Average Weight: 22255.9518 Da

Sequences

Not Available

Synonyms

Somatrem
Somatrem (genetical recombination)

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Pharmacology

Indication

Somatrem is a recombinant human growth hormone indicated for: (a) treatment of paediatric patients with growth failure due to growth hormone deficiency (GHD), (b) treatment of paediatric patients with growth failure due to idiopathic short stature (ISS), (c) treatment of paediatric patients with growth failure due to Turner syndrome (TS), (d) treatment of paediatric patients with growth failure due to chronic kidney disease (CKD) up to the time of renal transplantation, (e) treatment of adults with childhood-onset GHD, or (f) treatment of adults with adult-onset GHD ^Label.

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Contraindications & Blackbox Warnings

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Pharmacodynamics

In vitro and in vivo preclinical and clinical testing have demonstrated that somatrem is therapeutically equivalent to pituitary derived human growth hormone (hGH) ^2,Label. Paediatric patients who lack adequate endogenous growth hormone secretion, patients with chronic kidney disease, and patients with Turner syndrome that were treated with somatrem resulted in an increase in growth rate and an increase in insulin-like growth factor (IGF-1) levels similar to that seen with patients who possess endogenous pituitary derived hGH ^2,Label. With normalized levels of growth hormone and related mediator agents like IGF-1, patients demonstrate normalized skeletal, cell, organ, and overall tissue growth ^2,Label.

Mechanism of action

Somatrem - as well as endogenous growth hormone - binds to dimeric growth hormone (GH) receptors located within the cell membranes of target tissue cells resulting in intracellular signal transduction and a host of pharmacodynamic effects ^2,Label. Some of these pharmacodynamic effects are primarily mediated by insulin like growth factor (IGF-1) produced in the liver and also locally (ie. skeletal growth, protein synthesis), while others are primarily a consequence of the direct effects of somatropin (ie. lipolysis) ^2,Label.

Skeletal growth is accomplished at the epiphyseal plates at the ends of growing bone ^Label. Growth and metabolism of epiphyseal plate cells are directly stimulated by GH and its mediator IGF-I ^Label. Serum levels of IGF-I are low in children and adolescents who are growth hormone deficient, but increase during somatrem treatment ^Label. New bone is consequently formed at the epiphyses for paediatric patients in response to GH and IGF-I from somatrem treatment ^Label. This results in linear growth until these growth plates fuse at the end of puberty ^Label.

Somatrem treatment also causes an increase in both the number and the size of skeletal muscle cells ^Label. Additionally, such therapy also influences the size of internal organs, including kidneys, and increases red cell mass ^Label.

Linear skeletal bone growth is facilitated in part by GH-stimulated protein synthesis ^Label. This is demonstrated by nitrogen retention as reflected by a decline in urinary nitrogen excretion and blood urea nitrogen (BUN) during somatrem therapy ^Label. GH also acts as a modulator of carbohydrate metabolism which may improve a fasting hypoglycaemia feeling that some patients with inadequate GH secretion sometimes experience ^Label. Additionally, somatrem administration may decrease insulin sensitivity, resulting in increased serum fasting and postprandial insulin levels - usually more commonly in overweight or obese individuals, adults or children ^Label. Moreover, mean fasting and postprandial glucose and hemoglobin A1C levels remained in the normal range ^Label.

Furthermore, in growth hormone deficient patients, the use of somatrem resulted in lipid mobilization, reduction in body fat stores, increased plasma fatty acids, and decreased plasma cholesterol levels ^Label. Serum levels of inorganic phosphorus may increase slightly in patients with inadequate secretion of endogenous GH, chronic kidney disease, or Turner syndrome during somatrem therapy due to metabolic activity associated with bone growth as well as increased tubular reabsorption of phosphate by the kidney ^Label. Serum calcium is not significantly altered in somatrem patients ^Label. Sodium retention and increases in serum alkaline phosphatase can occur to patients taking somatrem ^Label. As well, GH can stimulate the synthesis of chondroitin sulphate and collagen as well as the urinary excretion of hydroxyproline ^Label.

Target	Actions	Organism
AGrowth hormone receptor	agonist	Humans
AInsulin-like growth factor 1 receptor	Not Available	Humans

Absorption

The absolute bioavailability of somatrem after subcutaneous administration in healthy adult males has been determined to be 81 +/- 20%. Additionally, as the subcutaneous terminal half-life is significantly longer than the intravenous terminal half-life, it appears as if the subcutaneous absorption of somatrem is slow and rate-limiting ^2,Label.

Volume of distribution

Animal studies with somatrem showed that growth hormone localizes to highly perfused organs, particularly the liver and kidney ^2,Label. The volume of distribution at steady state for somatrem in health adult males is approximately 50 mL/kg body weight, approximating the serum volume ^2,Label.

Protein binding

Not Available

Metabolism

Both the liver and kidney have been shown to be important metabolizing organs for growth hormone ^2,Label. Animal studies suggest that the kidney is the dominant organ of clearance. Growth hormone is filtered at the glomerulus and reabsorbed in the proximal tubules ^2,Label. It is then cleaved within renal cells into its constituent amino acids, which return to the systemic circulation ^2,Label.

Route of elimination

Animal studies suggest that the kidney is the dominant organ of clearance ^2,Label.

Half-life

The mean terminal half-life after subcutaneous administration is 2.1 +/- 0.43 hours while the mean terminal half-life after intravenous administration is determined to be 19.5 +/- 3.1 minutes ^2,Label.

Clearance

The clearance of somatrem after intravenous administration in healthy adults and children is reported to be in the range of 116-174 mL/hr/kg ^2,Label.

Adverse Effects

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Toxicity

Short-term overdosage with somatrem may initially result in hypoglycaemia and then subsequently to hyperglycemia ^2,Label. Moreover, this kind of short-term overdosage with somatrem is also likely to cause fluid retention ^2,Label.

Long-term overdose with somatrem could leads to signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess growth hormone ^2,Label.

Some animal based oral LD50 values have been reported as: mouse = 300mg/kg, rabbit = 3200 mg/kg, rat = 980 mg/kg.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Acarbose	Somatrem may decrease the hypoglycemic activities of Acarbose.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Somatrem.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Somatrem.
Acetohexamide	Somatrem may decrease the hypoglycemic activities of Acetohexamide.
Acyclovir	The metabolism of Acyclovir can be increased when combined with Somatrem.

Food Interactions

Not Available

Products

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Protropin - Kit Im Sc 10mg/vial	Somatrem (10 mg / kit) + Water (10 mL / kit)	Liquid; Powder, for solution	Intramuscular; Subcutaneous	Hoffmann La Roche	1998-05-13	2005-02-16
Protropin - Kit Im Sc 5mg/vial	Somatrem (5 mg / kit) + Water (10 mL / kit)	Liquid; Powder, for solution	Intramuscular; Subcutaneous	Hoffmann La Roche	1998-06-29	2003-07-30
Protropin Inj Pws 10mg/vial	Somatrem (10 mg / kit) + Water (20 mL / kit)	Liquid; Powder, for solution	Intramuscular	Genentech, Inc.	1992-12-31	1998-08-12
Protropin Pws 5mg/vial	Somatrem (5 mg / kit) + Water (10 mL / kit)	Powder, for solution	Intramuscular	Genentech, Inc.	1986-12-31	1998-07-14

Chemical Identifiers

UNII: CU8D464EDW
CAS number: 82030-87-3

References

General References

Allen DB, Fost N: hGH for short stature: ethical issues raised by expanded access. J Pediatr. 2004 May;144(5):648-52. doi: 10.1016/j.jpeds.2004.02.028. [Article]
Human Growth Hormone: Protropin [Link]

External Links

KEGG Drug: D05884
PubChem Substance: 347910403
RxNav: 56570
Wikipedia: Somatrem

FDA label

Download (420 KB)

MSDS

Download (78.8 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
Not Available	Completed	Not Available	Growth Disorders	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Liquid; powder, for solution	Intramuscular; Subcutaneous
Liquid; powder, for solution	Intramuscular
Powder, for solution	Intramuscular

Prices

Not Available

Patents

Not Available

Properties

State: Liquid
Experimental Properties: Not Available

Targets

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Details1. Growth hormone receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Protein kinase binding
Specific Function: Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).The soluble form (GHBP) acts as a rese...
Gene Name: GHR
Uniprot ID: P10912
Uniprot Name: Growth hormone receptor
Molecular Weight: 71498.885 Da

Details2. Insulin-like growth factor 1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes

General Function: Protein tyrosine kinase activity
Specific Function: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involv...
Gene Name: IGF1R
Uniprot ID: P08069
Uniprot Name: Insulin-like growth factor 1 receptor
Molecular Weight: 154791.73 Da

Drug created at September 16, 2015 20:43 / Updated at February 21, 2021 18:52

Somatrem

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets