Effect of Renal Failure on Pharmacokinetics of Carbamazepine in Rabbits

카르바마제핀의 체내동태에 대한 신장해의 영향

The pharmacokinetics of carbamazepine(100 mg/kg, oral) in the folic acid-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folic acid (50, 100, and 200 mg/kg). At folic acid dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and area under the plasma level-time curve (AUC) of carbamazepine increased significantly at folic acid dose of 100 and 200 mg/kg. The elimination rate constant (Kel) of carbamazepine decreased significantly, and half-life $(t_{1/2})$ of carbamazepine increased significantly at folic acid dose of 100 and 200 mg/kg. The serum creatinine concentration (Scr) correlated well with AUC and elimination rate constant (Kel) of carbamazepine, as well as BUN with AUC and elimination rate constant (Kel) of carbamazepine. These results suggest that adjustment of the dosage regimen of carbamazepine is desirable, and serum creatinine concentration (Scr) as well as BUN can be used for adjusting the dosage regimen of carbamazepine in renal failure.