Glucagon for Injection - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
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Glucagon for Injection - Scientific Information

Manufacture: Fresenius Kabi USA, LLC
Country: United States
Condition: Diagnosis and Investigation, Hypoglycemia
Class: Glucose elevating agents
Form: Liquid solution, Intramuscular (IM), Intravenous (IV)
Ingredients: Glucagon hydrochloride, lactose monohydrate, hydrochloric acid, sodium hydroxide.

Description

Glucagon for Injection, for intravenous or intramuscular use, is a gastrointestinal motility inhibitor that is produced by solid phase peptide synthesis. Glucagon is a singlechain polypeptide containing 29 amino acid residues. The chemical structure of the glucagon polypeptide is identical to human glucagon and to glucagon extracted from beef and pork pancreas. The structure of glucagon is:

Glucagon for Injection is a sterile, lyophilized white powder in a 3 mL vial. The reconstituted solution contains 1 mg of glucagon as hydrochloride per mL and lactose monohydrate (107 mg). Glucagon for Injection is supplied at pH 2.5 to 3.5 and is soluble in water.

Clinical Pharmacology

Mechanism of Action

Extra hepatic effects of glucagon include relaxation of the smooth muscle of the stomach, small bowel, and colon.

Pharmacodynamics

Table 3 displays the pharmacodynamics properties of Glucagon for Injection as a diagnostic aid during radiologic examination.

Table 3: Pharmacodynamic Properties of Glucagon for Injection as a Diagnostic Aid
Route of
Administration
Dosea Time of Onset of Action for GI
Smooth Muscle Relaxation
Duration of Smooth
Muscle Relaxation
Intravenous 0.25 to
0.5 mg
45 seconds 9 to 17 minutes
Intramuscular 1 mg 8 to 10 minutes 12 to 27 minutes
2 mg 4 to 7 minutes 21 to 32 minutes

a Select from these doses based on type of diagnostic procedure, route of administration and procedure duration.

Pharmacokinetics

Absorption

Following intramuscular administration of 1 mg dose, the maximum plasma glucagon concentrations of 3391 pg/mL were attained approximately 10 minutes after dosing.

Metabolism

The mean apparent halflife of glucagon was 26 minutes after intramuscular administration.

Glucagon is degraded in the liver, kidney, and plasma.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long term studies in animals to evaluate carcinogenic potential have not been performed.

Mutagenesis

Synthetic glucagon was negative in the bacterial reverse mutation assay (Ames test). The clastogenic potential of synthetic glucagon in the Chinese Hamster Ovary (CHO) assay was positive in the absence of metabolic activation. Doses of 100 and 200 mg/kg of glucagon of both pancreatic and recombinant origins gave slightly higher incidences of micronucleus formation in male mice but there was no effect in females. The weight of evidence indicates that synthetic and recombinant glucagon are not different and do not pose a genotoxic risk to humans.

Impairment of Fertility

Glucagon (rDNA and synthetic origin) was not tested in animal fertility studies. Studies in rats have shown that pancreatic glucagon does not cause impaired fertility.