CONCENTRATION-EFFECT AND CONCENTRATION-TOXICITY RELATIONS WITH LAMOTRIGINE - A PROSPECTIVE-STUDY

This prospective study was designed to ascertain whether measurement o f lamotrigine (LTG) concentrations in the epilepsy clinic could be use d to predict the onset of complete seizure control or the emergence of adverse effects. LTG was initiated in doses of 25 or 50 mg daily in 6 9 patients with newly diagnosed or poorly controlled epilepsy and was increased monthly in 50-mg increments until the patient became seizure -free for at least 6 months or developed adverse effects that abated a fter a reduction in dosage. LTG and other antiepileptic drug (AED) con centrations were measured at each clinic visit but were not supplied t o the investigator examining the patients. Overall, 19 patients either withdrew due to lack of efficacy or defaulted from the clinic. Of the remaining 50 patients, 32 (19 monotherapy, 13 polytherapy) became sei zure-free at widely varying daily LTG doses (median 200 mg, range 25-8 50 mg) and concentrations (median 3.8 mg/L, range 1.4-18.7 mg/L). Like wise, the 18 patients (5 monotherapy, 13 polytherapy) who experienced intolerable side effects showed substantial variations in daily LTG do ses (median 300 mg, range 100-900 mg) and concentrations (median 4.0 m g/L, range 0.4-18.5 mg/L). No useful concentration-effect or concentra tion-toxicity relation with LTG could be demonstrated in this study; t herefore, we believe that routine therapeutic drug monitoring with thi s new AED is not currently indicated.