Investigation of valproic acid-carbamazepine interaction by mixed effect modeling in Chinese epilepsy patients

OBJECTIVE To investigate the valproic acid-earbamazepine interaction in Chinese epilepsy patients. METHODS Nonlinear mixed effects modeling was used to estimate the effects of valproic acid-carbamazepine interaction on their clearance from 722 patients who received valproic acid and/or carbamazepine during their clinical routine care. RESULTS The final model describing VPA clearance was: CL = 0.0072 6 × TBW0.890× (1 + 18.1 DOSE) × 1.36GBZ× 1.22CHILD . The final model describing CBZ clearance was: CL = 1.21× DOSE0.409 ×TBW0.292 × 1.16VPA ×0.845ELDER. Where CL was clearance (L.h-1 ), TBW was total body weight (kg), DOSE was daily dosage (g.d-1. kg~ ) . CBZ = 1 for concomitant administration of CBZ and CBZ = 0 for otherwise; VPA = 1, when VPA dose was higher than 19 mg.kg -1 . CHILD for children less than 6 year and ELDER for people greater than 65 year. CONCLUSION Concomitant adminstration of valproic acid and carbamazepine resulted in 36% increase in valproic acid clearance and 16% increase in carbamazepine clearance when valproic acid daily dose was greater than 19 mg.kg-1 .