The influence of experimental spinal cord injury on carbamazepine pharmacokinetics. 2006

Hamed Reihani-Kermani, and Mehdi Ansari, and Saeid Karamousian
Department of Neurosurgery, Bahonar Hospital, Kerman, Iran. hreihani@kmu.ac.ir

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013119 Spinal Cord Injuries Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.). Myelopathy, Traumatic,Injuries, Spinal Cord,Post-Traumatic Myelopathy,Spinal Cord Contusion,Spinal Cord Laceration,Spinal Cord Transection,Spinal Cord Trauma,Contusion, Spinal Cord,Contusions, Spinal Cord,Cord Contusion, Spinal,Cord Contusions, Spinal,Cord Injuries, Spinal,Cord Injury, Spinal,Cord Laceration, Spinal,Cord Lacerations, Spinal,Cord Transection, Spinal,Cord Transections, Spinal,Cord Trauma, Spinal,Cord Traumas, Spinal,Injury, Spinal Cord,Laceration, Spinal Cord,Lacerations, Spinal Cord,Myelopathies, Post-Traumatic,Myelopathies, Traumatic,Myelopathy, Post-Traumatic,Post Traumatic Myelopathy,Post-Traumatic Myelopathies,Spinal Cord Contusions,Spinal Cord Injury,Spinal Cord Lacerations,Spinal Cord Transections,Spinal Cord Traumas,Transection, Spinal Cord,Transections, Spinal Cord,Trauma, Spinal Cord,Traumas, Spinal Cord,Traumatic Myelopathies,Traumatic Myelopathy
D013904 Thoracic Vertebrae A group of twelve VERTEBRAE connected to the ribs that support the upper trunk region. Vertebrae, Thoracic

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