Factors Influencing the Serum Levels of Carbamazepine and Carbamazepine-10, 11-Epoxide

Abstract

Carbamazepine-1 0, 11-epoxide(CBZ-Epox). a metabolite of carbamazepins (CBZ), IS known to have toxic effects as well as some antiepileptic property similar to CBZ. The serum levels of CBZ and CBZ-Epox at the steady state were measured by HPLC assay for 141 children and young adults (1-29 years) who were on CBZ monotherapy or In combination with other antiepileptic drugs. Eighty patients were on CBZ monotherapy. In addition to CBZ, 20 patients were on ethosuximide, eight on valproate. eight on phenytoin, five on phenobarbital or prrmidone and 20 on more than one additional antrepileptic drug. In patients on CBZ monotherapy, the mean CBZ level was 8.2 ug/ml ± 22 ( ± SE), the CBZ-Epox level was 1.6 ug/ml ± 0.6 and the CBZ-Epox/CBZ ratio was 0.19±05 On univariate analysis, factors that significantly' influenced the CBZ-Epox/CBZ ratio were the age of the patient, the time Interval between the last dose and blood sampling, and the dose/surface area. Multivarrate analysis demonstrated that the only factors that significantly' influenced the CBZ-Epox/CBZ ratio were the time interval between the last doe and blood sampling and the age of the patients Patients on polytherapy had significantly' higher CBZ-Epox / CBZ ratios than patients on monotherapy. The ratios were as follows: CBZ and ethosuximide, 0.23 ± 005; CBZ and valproate, 0.33 ± 0.15; CBZ and phenytoin, 0.35 ± 011; CBZ and phenobarbital or primidone, 0.29 ± 0.05; CBZ and more than one additional anticonvulsant, 0.44 ± 017 CBZ and CBZ-Epox levels are invarrably affected by the age of the patients. the CBZ dose and co-medication with other annepileptrc durgs. Careful monitoring IS mandatory in the latter group to avoid toxicity 'p < 001, unpaired t-test