ETHOSUXIMIDE PLASMA LEVELS ARE RELATED TO DOSE

And are altered by age and associated therapy There are conflicting reports on the effects of age and associated antiepileptic therapy on ethosuximide plasma levels in patients

being treated for absence seizures. This Italian study retrospectively analysed the data obtained over a 2-year period during the

treatment of 198 epileptic patients. 39 patients received ethosuximide alone and !59 patients received it in combination with other

antiepileptic drugs. No other drugs were taken and oral doses of ethosuximide were 4-85mg/ kg. Ethosuximide plasma concentration (J.lg/ml) to daily dose (mg/kg) ratio is defined as the LID ratio. Patients were divided into 3

age groups: children, 2.5-9 years (48 patients); adolescents, I 0-15 years (79 patients) and adults, 16-34 years (71 patients). LID

ratios for each group were 2.23, 3.14 and 3.34, respectively. The ratio in children was significantly lower than in the other two

groups. For each age group there was a significant correlation between ethosuximide plasma concentration and daily oral dose but

there was such a wide scattering of results that it could be of no predictive value. The slope of the linear regression lines obtained

for the adult group was significantly different from that of the other 2 groups. The mean LID ratio for patients taking ethosuximide alone was 3.66 (39 patients), in combination with phenobarbitone it was 3.19 (71 patients), with carbamazepine 2.87 ( 14 patients), with 2 other antiepileptics 2.64 (3 3 patients), with phenytoin 2.61 (7

patients), with primidone 2.4 7 (29 patients) and with valproic acid 2.35 (5 patients). Associated therapy always reduced the LID

ratio, but this was significant only for primidone, valproic acid and treatment with 2 other anticonvulsants. When analysing the

effect of age and associated treatment, the Ll D ratio always tended to increase with age. The difference between the child and

adolescent group is significant when treated with ethosuximide alone or in combination with primidone. Within an age group

there was always a tendency towards decreased LID ratio with associated therapy. The decrease was significant in the child group

for primidone; in the adolescent group for phenobarbitone, carbamazepine, primidone and 2 other anticonvulsants and in the adult group for primidone and 2 other anticonvulsants.

In conclusion, although ethosuximide plasma concentration is related to dose, it can be of no value as a guide to prescribing the

drug. Both age and po!ytherapy decrease the LID ratio: most significantly in children and in combination with primidone. Since

the therapeutic ethosuximide plasma concentration is between 40-1 OOpg/ ml, monitoring of plasma levels is essential to optimise a dose regimen, especially in combination therapy and in children. Battino, D. et al.: Clinical Pharmacokinetics 7: 176 (Mar-Apr 1982)

0156-2703/82/0501-0015/0$01.00/0 © ADIS Press INPHARMA 1 May 1982 15