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 micrograms/ml to a postinduction level of 26.8 +/- 5.2 micrograms/ml on study day 28. Ethosuximide clearance increased (alpha = 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 mean - 53.7 +/- 11.5 hr (before induction) to mean = 44.6 +/- 10.7 hr (after induction); the difference between some subjects was large. These data show that ethosuximide disposition is altered by carbamazepine.