Association of drug levels & pharmacokinetics of carbamazepine with seizure control.

BACKGROUND & OBJECTIVES: A sizeable number of epilepsy patients remain uncontrolled with carbamazepine (CBZ) monotherapy. While the therapeutic plasma concentration range of CBZ is only vaguely defined, pharmacokinetic differences in the disposition of CBZ among subjects could be responsible for the inadequate control of seizures in some. This study was aimed at associating serum CBZ levels with seizure control and elucidating any pharmacokinetic differences between patients with controlled and uncontrolled epilepsy. METHODS: The study was conducted in 16 controlled and 15 uncontrolled adult epileptic patients receiving CBZ monotherapy for the previous 3 or more months, without any dosage change. Blood samples were drawn from the patients before and 0.5, 1, 2, 3, 4, 8, 12 and 24 h after ingestion of their total daily dose of CBZ. Serum CBZ levels were measured by HPLC and the pharmacokinetic parameters were calculated. RESULTS: The uncontrolled epileptic patients were receiving a higher daily dose of CBZ (difference not significant). The trough and peak serum CBZ levels were relatively higher in the uncontrolled group, and at no time point were the drug levels lower in these patients compared to the controlled group. The absorption kinetics, volume of distribution and plasma half life of CBZ were similar in the two groups. Thus, non-attainment or non-maintenance of therapeutic CBZ level or other pharmacokinetic difference was not responsible for occurrence of seizures in the uncontrolled patients. A high percentage of patients with generalised tonic clonic seizures (73%) and simple partial seizures (SPS) with generalisation (66%) were controlled by CBZ, while SPS and complex partial seizures (CPS) were largely uncontrolled. INTERPRETATION & CONCLUSIONS: It appears that pharmacodynamic resistance of the seizure to CBZ rather than pharmacokinetic factors is responsible for lack of efficacy of CBZ in nonresponding epileptic patients.