Kinetics of a carbamazepine‐ethosuximide interaction

Carbamazepine and ethosuximide are used together to treat epileptic mixed‐seizure patterns. Since carbamazepine has been shown to induce drug‐metabolizing enzyme(s) in the liver, it follows that carbamazepine may alter ethosuximide disposition. Six normal subjects took one 250‐mg ethosuximide capsule twice each day for 55 consecutive doses (study days 1 to 28) and one 200‐mg carbamazepine tablet each evening from study days 11 to 27. Plasma samples were collected on study days 10, 17, 21, and 28. Mean steady‐state concentrations of ethosuximide declined by 17% from a preinduction (study day 10) level of 32.2 ± 5.6 μg/ml to a postinduction level of 26.8 ± 5.2 μg/ml on study day 28. Ethosuximide clearance increased (α = 0.05) between study days 10 and 28 from 0.664 ± 0.120 to 0.800 ± 0.0154 l/hr. The time course of induction was analyzed using a kinetic induction theory. Ethosuximide half‐life was lowered from x̄ = 53.7 ± 11.5 hr (before induction) to x̄ = 44.6 ± 10.7 hr (after induction); the difference between some subjects was large. These data show that ethosuximide disposition is altered by carbamazepine. Clinical Pharmacology and Therapeutics (1980) 28, 646–651; doi: 10.1038/clpt.1980.216