Topamax

Pharmacokinetics

The absorption of topiramate is rapid and nearly complete. Topiramate is poorly bound (9–17%) to plasma proteins. Both renal and hepatic elimination occurs. In the absence of enzyme induction, more than 80% of a single radiolabeled dose of topiramate is excreted unchanged in the urine.37

Effect of liver disease

The effect of liver impairment on the metabolism of topiramate was evaluated in patients with moderate to severe hepatic impairment as defined by Child-Pugh.1 When compared to healthy subjects, the plasma clearance was reduced by 26% and the half-life was prolonged by 36%.38 Both these results were clinically insignificant, but these changes may be clinically significant in selected patients. Liver disease would not be expected to cause significant changes in the protein binding of topiramate. Because the protein binding of topiramate is only 9–17% and the alteration in metabolism by liver disease is not clinically significant, dosage adjustments are not required for patients with liver disease.

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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