Eutropin S Pen Injection Mechanism of Action

Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, somatropin and somatropin agonists. ATC code: H01AC01.
Recombinant Human Growth Hormone.
Pharmacology: Pharmacodynamics: Mechanism of action: Somatropin is a polypeptide hormone made up of 191 amino acids made by recombinant DNA technology, and promotes the growth of cells, particularly bones, synthesizes protein necessary for growth, and stimulates adipolysis.
Clinical efficacy and safety: A total of three clinical tests were conducted to verify the efficacy of this drug. This drug was administered to children with growth hormone deficiency, Turner's syndrome, as well as small for gestational age (SGA).
To evaluate its efficacy, 0.15 IU/kg of this drug was administered to children with growth hormone deficiency three times a week for 12 months. A total of 20 children (average age: 10.2), were evaluated for efficacy such as height velocity that was measured before treatment and every three months after treatment. Height velocity increased from an average of 3.20±1.21 cm/year before treatment to 9.60±2.85 cm/year, 8.55±2.28 cm/year, 7.48±1.32 cm/year, and 7.22±1.46 cm/year, at three, six, nine and 12 months after treatment, respectively. IGF-1 concentration rose from 18.6±5.5 nMol/L before treatment to 26.5±8.8 nMol/L and 35.8±12.7 nMol/L at six and 12 months after treatment, respectively.
After administering this drug to children with Turner's syndrome, an open-label, single -arm, clinical trial was conducted before and after administration to assess its efficacy. Sixty children with Turner's syndrome whose chronological age is under 14 and whose height is less than 1 SD than the average for the same age (average chronological age: about 10.8) received about 1 IU/kg per week six to seven times a week for one year. For 50 of these children, standard deviation scores (SDS) of height, height velocity, weight SDS for chronological age (CA), weight SDS for height, ratio of height age to bone age, and IGF-1 were measured to evaluate efficacy before and after treatment. The height curve and height velocity curve showed that height SDS rose by about 0.5 one year after treatment, height velocity for 88% of patients increased by more than 2 SD (standard deviation), and height velocity for 98% of patients rose by more than 1 SD. (See Tables 1 and 2.)

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An open-label, single-arm, phase III clinical trial was conducted to assess the efficacy of about 0.48 mg/kg/week of this drug administered to prepubertal SGA for six months. During the clinical trial of 30 patients, the difference in height velocity before and after six months of treatment was compared through four visits (screening, Day 0, 3 months, and 6 months). The difference in height velocity before and after treatment in the PP group analysis was statistically significant (5.30±1.84 cm/year, p<0.0001), and the lower limit of the 95% one-sided confidence interval was 4.55 cm, larger than the predetermined level of 2 cm. This showed that the administration of about 0.48 mg/kg/week of this drug to prepubertal SGA for six months led to the improvement of height velocity.
Pharmacokinetics: Intramuscular injection or subcutaneous injection of 0.1 IU of this drug per kg of body weight was applied to children with growth hormone deficiency.
T_max: 27±0.3 hours for intramuscular injection, and 5.3±0.3 hours for subcutaneous injection.
Clearance: 24.5 L/hr for intramuscular injection, and 27.2 L/hr for subcutaneous injection.
Half-life: 1.99 hours for intramuscular injection, and 2.39 hours for subcutaneous injection.
Absorption constant rate: 0.47/hr for intramuscular injection, and 0.40/hr for subcutaneous injection.
Elimination constant rate: 0.35/hr for intramuscular injection, and 0.29/hr for subcutaneous injection.
Toxicology: Preclinical Safety Data: Non-clinical data showed that this drug does not have a particular risk to people based on the results of traditional tests related to safety pharmacology, acute toxicity, repeated-dose toxicity, genotoxicity, local tolerance, immune toxicity and reproductive toxicity. A carcinogenicity test was not performed for this drug.
Subcutaneous injection of 40 IU/kg in mice did not have a neurological affect. Intravenous injection of 20 IU/kg in rabbits did not have cardiovascular or respiratory affects.
In acute toxicity studies where intramuscular injections of 40 IU/kg and subcutaneous injections of 80 IU/kg were made in rats and mice, toxicity due to the drug was not detected.
In repeated subcutaneous injections of up to 10 IU/kg/day in mice for 90 days, only the high-dose injection group (10 IU/kg/day, more than 60 times the clinical dose) showed various kinds of toxicity symptoms such as death, reduced activity, and dyspnea. The same trial for rats did not produce toxicity symptoms in all-dose groups.
Genotoxicity of this drug was not observed in a bacterial reverse mutation test, in vitro chromosomal aberration assay, and in vivo micronucleus assay for mice.
Local tolerance and immunogenicity test results showed that this drug does not cause particular hazards for people.
In a fertility and early embryonic development toxicity test, embryo-fetal developmental toxicity test and prenatal & postnatal toxicity test for rats with subcutaneous injections of up to 10 IU/kg/day, reproductive hazards were not observed. The embryo-fetal developmental toxicity test for rabbits with subcutaneous injection of the same dose also did not produce reproductive risks.