Abstract
Objectives: To investigate the pharmacokinetics of Carbamazepine (CBZ) in rats during growth hormone treatment. Methods: Recombinant Human Growth Hormone (rhGH) was injected subcutaneously at a daily dose of 0.1 mg/ kg, 2 mg/kg, or phosphate buffered saline (control) for 5 days in male Sprague-Dawley rats. On day 6, a dose of 25 mg/kg of CBZ was injected intravenously via a jugular vein cannula into the rat. Growth rate were compared between treatment groups. The pharmacokinetics of CBZ was determined from its concentrations in rats’ blood and urinary samples. Results: Over the 5-day treatment period, growth rate were greater than control for the 2 mg/kg rhGH dosed group. The volume of distribution (Vss) was significantly (p<0.05) decreased in the high dosed rhGH rats compared to the control group. Total body clearance (CL) in the 2 mg/kg rhGH group was also significantly (p<0.05) decreased compared with the control group (0.497 ± 0.076 L/hr/kg vs 0.685 ± 0.109 L/hr/kg). Urinary data showed that renal and metabolic clearances were both significantly (p<0.05) decreased in the 2 mg/kg rhGH group. Conclusions: A dose dependent effect of rhGH was observed on growth rates and CBZ pharmacokinetics in rats. After 5 days rhGH treatment, the volume of distribution of CBZ was significantly changed in the 2 mg/kg/day rhGH treated groups. In the 2 mg rhGH/kg treated rats, both renal and metabolic clearance of CBZ were also significantly decreased compared with the control group. Similar decreases in volume of distribution and both clearances may suggest the interaction may involve increased CBZ plasma protein binding during rhGH treatment in rats.
Highlights
Human Growth Hormone is secreted by somatotrophs of the anterior pituitary and produced by monocytes
It is reported that Recombinant Human Growth Hormone (rhGH) alters the muscle/fat ratio as a consequence of increasing protein synthesis, lipolysis, and fatty acids oxidation and affects hepatic enzymes activity [1,2,3,4,5,6,7]
There are several studies examining drug metabolizing enzyme changes following rhGH, there is little known with regard to induced pharmacokinetic changes
Summary
Human Growth Hormone (hGH) is secreted by somatotrophs of the anterior pituitary and produced by monocytes It can stimulate the rate of protein synthesis in cells, increase the number of cells, and increase the growth of numerous tissues in the body. Somatropine (Humatrope® by Eli Lilly) is a Recombinant Human Growth Hormone (rhGH) synthesized by Escherichia coli using genetic engineering techniques. It was approved by the FDA for the treatment of pituitary dwarfism in children, Turner’s syndrome and other forms of growth retardation, as well as HIV-associated wasting. There are several studies examining drug metabolizing enzyme changes following rhGH, there is little known with regard to induced pharmacokinetic changes
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