Clinical study of lamotrigine and valproic acid in patients with epilepsy:Using a drug interaction to advantage?

Lamotrigine (LTG) is one of the newer antiepileptic drugs which has been sh own to have a spectrum of drug interactions (including with other epilepsy drugs) that can have a pronounced effect on LTG kinetics. The present study examined the LTG metabolic inhibition dose-response relationship with valp roic acid (VPA) in eight patients with epilepsy with a view to using this t o benefit the patient. This could benefit the patient not only by attaining higher plasma LTG concentrations with "standard" dosages of LTG, but also possibly by achieving better seizure control through providing a less varia ble peak-to-trough fluctuation in LTG concentrations as a result of extendi ng the half-life of LTG. The dosages of VPA trialed were 0, 200, 500, and 1 ,000 mg/d which resulted in a mean increase in LTG area under the curve of 83.7 +/- 14.7% at 200 mg VPA/d, to and 160 +/- 37.9% at 1,000 mg VPA/d. The presence of concomitant enzyme inducers in some patients did not influence the percentage increase from baseline in half-life observed, although clea rly those on inducers started from a lower absolute half-life as a result o f the induction. The effect was shown to be quite variable, particularly at the highest dosage of VPA tested (1,000 mg/d), suggesting that this effect could be best applied with the support of the therapeutic drug monitoring laboratory determining plasma LTG concentrations to allow individualization of the LTG dosage.