Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Somatropin and somatropin agonists
ATC code: H 01 AC 01
Pharmacodynamic properties:
Identical to pituitary-derived human growth hormone (pit-hGH) in amino acid sequence, chain length (191 amino acids) and pharmacokinetic profile. Zomacton can be expected to produce the same pharmacological effects as the endogenous hormone.
Skeletal system:
Growth hormone produces a generally proportional growth of the skeletal bone in man. Increased linear growth in children with confirmed deficiency of pit-hGH has been demonstrated after exogenous administration of Zomacton. The measurable increase in height after administration of Zomacton results from an effect on the epiphyseal plates of long bones. In children who lack adequate amounts of pit-hGH, Zomacton produces increased growth rates and increased IGF-1 (Insulin-like Growth Factor/Somatomedin-C) concentrations that are similar to those seen after therapy with pit- hGH. Elevations in mean serum alkaline phosphatase concentrations are also involved.
Other organs and tissues:
An increase in size, proportional to total increase in body weight, occurs in other tissues in response to growth hormone, as well. Changes include: increased growth of connective tissues, skin and appendages; enlargement of skeletal muscle with increase in number and size of cells; growth of the thymus; liver enlargement with increased cellular proliferation; and a slight enlargement of the gonads, adrenals, and thyroid.
Disproportionate growth of the skin and flat bones and accelerated sexual maturation have not been reported in association with the growth hormone replacement therapy.


Protein, carbohydrate and lipid metabolism:
Growth hormone exerts a nitrogen-retaining effect and increases the transport of amino acids into tissue. Both processes augment the synthesis of protein. Carbohydrate use and lipogenesis are depres- sed by growth hormone. With large doses or in the absence of insulin, growth hormone acts as a diabetogenic agent, producing effects seen typically during fasting (i.e. intolerance to carbohydrate, inhibition of lipogenesis, mobilisation of fat and ketosis).
Mineral metabolism:
Conservation of sodium, potassium, and phosphorous occurs after treatment with growth hormone.
Increased calcium loss by the kidney is offset by increased absorption in the gut. Serum calcium concentrations are not significantly altered in patients treated with Zomacton or with pit-hGH.
Increased serum concentrations of inorganic phosphates have been shown to occur both after Zomacton and pit-hGH. Accumulation of these minerals signals an increased demand during tissue synthesis.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Twenty-four (24) healthy adult subjects received 1.67 mg somatropin either by conventional S.C.
injection or by ZomaJet needle free device. Peak plasma levels of around 20 ng/ml were observed 3.5 to 4 hours after administration of the medicinal product.
A terminal half-life 2.6 hours was observed when the compound was administered with Zomajet needle-free device which is likely to be due to a rate limiting absorption process.
Data from other somatropin containing products suggest that the bioavailability subcutaneously administered somatropin is approximately 80% in healthy adults and that both liver and kidney have been shown to be important protein catabolism organs eliminating the compound.