| OBSERVATION'S |
Topiramate, an anticonvulsant drug used in the treatment of epilepsy, is a sulfamate-substituted monosaccharide, structurally dissimilar to other standard anticonvulsant drugs.1,2 Topiramate is routinely administered orally, absorbed rapidly and metabolized minimally. Peak plasma concentrations are reached 2-3 hours after dosing. Binding to plasma proteins is low, normally less than 15%. Elimination is predominantly renal as unaltered topiramate, with an elimination half-life of 20-30 hours. Plasma concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administrations topiramate, with exception in individual patients on phenytoin exhibiting increased phenytoin plasma concentrations after addition of topiramate. Co-administration of phenytoin or carbamazepine decreases topiramate plasma concentrations. Changes in co-therapy with phenytoin or carbamazepine (e.g., addition or withdrawal) for patients stabilized on topiramate therapy may require topiramate dose adjustment. As with other renally eliminated anticonvulsant drugs, patients with impaired renal function exhibit decreased renal clearance.3,4 The correlation between measurement of topiramate by the INNOFLUORR method and clinical outcome has not been established. The appropriate use of the result for patient evaluation must be determined by the clinician. However, a proportional increase in topiramate plasma concentration with dosage increase over the range of 200 to 800 mg/day was shown in pharmacokinetic studies of the drug. Gas chromatography has been used previously to quantitate circulating plasma levels of topiramate.5 Leppik IE. Antiepileptic drugs in development; Prospects for the near future. Epilepsia 1994; 35(suppl 4): S29-S40. Rogawski MA, Porter RJ. Antiepileptic drugs: Pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacological Reviews; 42(3): 223-286. Ben-Menachem E, Perucca E, Bourgeois BF, Shorvon SD, French J. Topamax, Topiramate, New Advances n the Treatment of Epilepsy. Abstracts, Oporto International Fairs, Oporto, Portugal 1994. Data on file, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA. Holland ML, Uetz JA, Ng KT. Automated capillary gas chromatographic assay using flame ionization detection for the determination of topiramate in plasma. Journal of Chromatography 1988; 433: 276-281. |
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