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Carbamazepine is an iminostilbene derivative related to the tricyclic antidepressants that is used in the treatment of tonic-clonic (grand mal), partial or secondarily generalized seizures (Table 11-1).1,2 Although methods have been suggested to treat acute seizures with carbamazepine, lack of an intravenous dosage form has limited its use in this area. Thus, the drug is used primarily as a prophylactic agent in the chronic therapy of epilepsy. Carbamazepine is also a useful agent to treat trigeminal neuralgia and bipolar affective disorders.2,3

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Table 11-1 International Classification of Epileptic Seizures with Treatment Recommendations39,40 
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The antiseizure activity of carbamazepine is related to its ability to decrease transmission in the nucleus ventralis anterior section of the thalamus, an area of the brain thought to be involved with the generalization and propagation of epileptic discharges.1,2 Although the exact cellular mechanism of action is unclear, inhibition of voltage-gated sodium channels appears to be involved. Additionally, carbamazepine depresses posttetanic potentiation and may prevent increases in cyclic adenosine monophosphate (cAMP).

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The accepted therapeutic range for carbamazepine is 4–12 μg/mL when the drug is used for the treatment of seizures. Carbamazepine plasma protein binding is quite variable among individuals because it is bound to both albumin and α1-acid glycoprotein (AGP). In patients with normal concentrations of these proteins, plasma protein binding is 75–80% resulting in a free fraction of drug of 20–25%.4–6 AGP is classified as an acute phase reactant protein that is present in lower amounts in all individuals but is secreted in large amounts in response to certain stresses and disease states such as trauma, heart failure, and myocardial infarction. In patients with these disease states, carbamazepine binding to AGP can be even larger resulting in an unbound fraction as low as 10–15%.

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Little prospective work has been done to establish the therapeutic range for unbound carbamazepine serum concentrations or the clinical situations where ...

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