Factors influencing serum levels of carbamazepine and carbamazepine-10,11-epoxide in children

• Published in: Epilepsy research Vol. 4; no. 1; pp. 72 - 80
• Main Authors: Altafullah, Irfan, Talwar, Dinesh, Loewenson, Ruth, Olson, Kay, Lockman, Lawrence A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.1989; Elsevier
• Subjects: Adolescent; Adult; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic drugs; Biological and medical sciences; Carbamazepine; Carbamazepine - analogs & derivatives; Carbamazepine - metabolism; Carbamazepine - pharmacokinetics; Carbamazepine - therapeutic use; Carbamazepine-10,11-epoxide; Child; Child, Preschool; Children; Drug Therapy, Combination; Epilepsy - drug therapy; Humans; Infant; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Children; Antiepileptic drugs; Carbamazepine; Carbamazepine-10,11-epoxide; Human; Drug combination; Epilepsy; HPLC chromatography; Anticonvulsant; Metabolism; Biological monitoring; Young adult; Serum; Ambulatory; Pharmacokinetics; Child; Age
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/0920-1211(89)90060-0

Carbamazepine-10,11-epoxide (CBZ-E), the principal metabolite of carbamazepine (CBZ), is reported to have antiepileptic and toxic effects similar to CBZ. Steady-state CBZ and CBZ-E levels (high performance liquid chromatography, HPLC assay) were reviewed in 225 outpatient children and young adults taking CBZ with or without other antiepileptic drugs (AEDs). In patients on CBZ alone, mean serum concentration of CBZ was 7.9 ± 1.9 μg/ml and of CBZ-E was 1.5 ± 0.6 μg/ml. The CBZ-E CBZ ratio was 19.6 ± 2.4%. Serum CBZ increased with increasing age and with CBZ dose. CBZ-E increased with increasing CBZ dose but was unaffected by age. The CBZ-E CBZ ratio progressively declined with age. Co-medication with barbiturates or valproic acid significantly increased CBZ-E. Phenytoin showed a similar trend while ethosuximide caused the least change. Patients on CBZ and two or more other AEDs had highest CBZ-E levels and CBZ-E CBZ ratio. CBZ and CBZ-E levels are variably affected by age, CBZ dose, and co-medication with other AEDs. When other AEDs are administered, careful monitoring is especially indicated in order to avoid toxicity.