The influence of experimental spinal cord injury on carbamazepine pharmacokinetics

Previous studies have demonstrated that pharmacokinetic behavior of several drugs such as paracetamol, theophylline, and aminoglycosides are significantly altered in patients with spinal cord injury. So far, no study on pharmacokinetics of carbamazepine has been performed in patients or experimental models with spinal cord injury. The present study was designed to find the influence of experimental spinal cord injury on carbamazepine pharmacokinetics.

Among 12 male albino rabbits, 6 were subjected to spinal cord injury at the 8th thoracic level by knife severance method and 6 rabbits underwent laminectomy alone (sham-lesioned control group). All received a single oral dose of carbamazepine (20 mg/kg) 24 hours after the injury. Blood samplings were done at predetermined times to 96 hours after drug administration. Carbamazepine concentration in serum samples was determined by high-performance liquid chromatography. Pharmacokinetic parameters including maximum concentration, time to reach maximum concentration, half-life, and area under the curve(0 - 24) were directly determined from the concentration-time curve. Area under the concentration against time curve 24-infinity was calculated from the real data.

Maximum concentration was appeared at 2.8 hours after administration in sham-lesioned control group at a concentration of 2.3 microg/mL, whereas in spinal cord injury group it was appeared at 4.4 hours at a concentration of 2.7 microg/mL. In spinal cord-injured group, area under the curve and half-life were increased from 29.1 microg/mL.hr to 38.7 microg/mL.hr and from 7.7 hr to 14.1 hr as compared with the sham-lesioned control group, respectively. Statistical analyses of data showed that spinal cord injury does not induce significant changes in carbamazepine pharmacokinetics.

We concluded that pharmacokinetic behavior of carbamazepine was not significantly changed by spinal cord injury, although its subtle pharmacokinetic changes could be resulted from alteration in gastrointestinal tract motility, blood perfusion, or metabolism.