Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

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. *Corresponding author: William R Ravis, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama 36849, USA, Tel: 334-844-8325; Fax: 334-844-8331; E-mail: [email protected] Received March 06, 2013; Accepted September 20, 2013; Published September 27, 2013 Citation: Lin YJ, Lee YHP, Ravis WR (2013) Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats. Clin Exp Pharmacol 3: 132. doi:10.4172/2161-1459.1000132 Copyright: © 2013 Lin YJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.