Tegretol, Carbatrol

Pharmacokinetics

The absorption of carbamazepine from immediate-release tablets is slow, erratic, and unpredictable. Absorption does not follow a simple first-order process. Absorption occurs faster from the syrup dosage form. A controlled-release dosage form and a sustained-release dosage form administered every 12 hours are bioequivalent to immediate-release tablets administered every 6 hours.

Carbamazepine is 75–85% bound to plasma proteins, including albumin and alpha glycoprotein. The free fraction is reported to be inversely related to the concentration of alpha glycoprotein.

Carbamazepine is extensively metabolized (primarily by CYP3A4) to an active metabolite, which is further metabolized. Carbamazepine induces its own metabolism.22-23

Effect of liver disease

Carbamazepine is a low-extraction drug but is extensively metabolized by the liver. Therefore, it is expected that the metabolism of carbamazepine is sensitive to decreased hepatic function but not to changes in hepatic blood flow. A reduction in protein binding can occur in patients with liver disease.24

Effect of GI disease

The effect of GI disease has not been studied in patients receiving carbamazepine. However, because carbamazepine is poorly water-soluble and the immediate-release tablet (Tegretol) results in erratic and prolonged absorption, it is likely that GI disease will alter carbamazepine absorption. Diseases that alter GI transit can affect the absorption of the osmotic-pump controlled-release preparation of carbamazepine (Tegretol-XR). In normal volunteers, Wilding demonstrated significant variability in GI transit time of the osmotic-pump controlled-release formulation, which resulted in variability in carbamazepine absorption.25 Absorption variability from the immediate-release tablets is also likely because the absorption is slow, erratic, and prolonged. Absorption from the suspension and the sustained-dosage form (Carbatrol) is unknown.

Adapted from: Garnett WR. Gastrointestinal and hepatic disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;63-74. 
With permission from Elsevier (www.elsevier.com). 

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Reviewed By: 
Steven C. Schachter, MD
on: 
Monday, March 1, 2004