"Jan. 8, 2013 -- People with epilepsy have a higher risk for migraines, and now new research offers evidence of a genetic link between the two conditions.
The study confirmed that having a strong family history of epilepsy is a strong "...
In controlled clinical trials, carbamazepine has been shown to be effective in the treatment of psychomotor and grand mal seizures, as well as trigeminal neuralgia.
Mechanism of Action
Carbamazepine has demonstrated anticonvulsant properties in rats and mice with electrically and chemically induced seizures. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. Carbamazepine greatly reduces or abolishes pain induced by stimulation of the infraorbital nerve in cats and rats. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Carbamazepine is chemically unrelated to other anticonvulsants or other drugs used to control the pain of trigeminal neuralgia. The mechanism of action remains unknown.
The principal metabolite of carbamazepine, carbamazepine-10,11-epoxide, has anticonvulsant activity as demonstrated in several in vivo animal models of seizures. Though clinical activity for the epoxide has been postulated, the significance of its activity with respect to the safety and efficacy of carbamazepine has not been established.
Taken every 12 hours, carbamazepine extended-release capsules provide steady state plasma levels comparable to immediate-release carbamazepine tablets given every 6 hours, when administered at the same total mg daily dose.
Following a single 200 mg oral extended-release dose of carbamazepine, peak plasma concentration was 1.9 ± 0.3 μg/mL and the time to reach the peak was 19 ± 7 hours. Following chronic administration (800 mg every 12 hours), the peak levels were 11.0 ± 2.5 μg/mL and the time to reach the peak was 5.9 ± 1.8 hours. The pharmacokinetics of extended-release carbamazepine is linear over the single dose range of 200-800 mg.
Carbamazepine is 76% bound to plasma proteins. Carbamazepine is primarily metabolized in the liver. Cytochrome P450 3A4 was identified as the major isoform responsible for the formation of carbamazepine-10,11-epoxide. Since carbamazepine induces its own metabolism, the half-life is also variable. Following a single extended-release dose of carbamazepine, the average half-life range from 35-40 hours and 12-17 hours on repeated dosing. The apparent oral clearance following a single dose was 25 ± 5 mL/min and following multiple dosing was 80 ± 30 mL/min.
After oral administration of 14C-carbamazepine, 72% of the administered radioactivity was found in the urine and 28% in the feces. This urinary radioactivity was composed largely of hydroxylated and conjugated metabolites, with only 3% of unchanged carbamazepine.
Carbamazepine-10,11-epoxide is considered to be an active metabolite of carbamazepine. Following a single 200 mg oral extended-release dose of carbamazepine, the peak plasma concentration of carbamazepine-10,11-epoxide was 0.11 ± 0.012 μg/mL and the time to reach the peak was 36 ± 6 hours. Following chronic administration of a extended-release dose of carbamazepine (800 mg every 12 hours), the peak levels of carbamazepine-10,11-epoxide were 2.2 ± 0.9 μg/mL and the time to reach the peak was 14 ± 8 hours. The plasma half-life of carbamazepine-10,11-epoxide following administration of carbamazepine is 34 ± 9 hours. Following a single oral dose of extended-release carbamazepine (200-800 mg) the AUC and Cmax of carbamazepine-10,11-epoxide were less than 10% of carbamazepine. Following multiple dosing of extended-release carbamazepine (800-1600 mg daily for 14 days), the AUC and Cmax of carbamazepine-10,11-epoxide were dose related, ranging from 15.7 μg.hr/mL and 1.5 μg/mL at 800 mg/day to 32.6 μg.hr/mL and 3.2 μg/mL at 1600 mg/day, respectively, and were less than 30% of carbamazepine. Carbamazepine-10,11-epoxide is 50% bound to plasma proteins.
A high fat meal diet increased the rate of absorption of a single 400 mg dose (mean Tmax was reduced from 24 hours, in the fasting state, to 14 hours and Cmax increased from 3.2 to 4.3 μg/mL) but not the extent (AUC) of absorption. The elimination half-life remains unchanged between fed and fasting state. The multiple dose study conducted in the fed state showed that the steady-state Cmax values were within the therapeutic concentration range. The pharmacokinetic profile of extended-release carbamazepine was similar when given by sprinkling the beads over applesauce compared to the intact capsule administered in the fasted state.
The effect of hepatic impairment on the pharmacokinetics of carbamazepine is not known. However, given that carbamazepine is primarily metabolized in the liver, it is prudent to proceed with caution in patients with hepatic dysfunction.
The effect of renal impairment on the pharmacokinetics of carbamazepine is not known.
No difference in the mean AUC and Cmax of carbamazepine and carbamazepine-10,11epoxide was found between males and females.
Carbamazepine is more rapidly metabolized to carbamazepine-10,11-epoxide in young children than adults. In children below the age of 15, there is an inverse relationship between CBZE/ CBZ ratio and increasing age.
No information is available on the effect of race on the pharmacokinetics of carbamazepine.
Last reviewed on RxList: 3/18/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Carbatrol Information
Carbatrol - User Reviews
Carbatrol User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find tips and treatments to control seizures.