August 1984

Interdosage Fluctuations in Plasma Carbamazepine Concentration Determine Intermittent Side Effects

Author Affiliations

From the Department of Neurology at the Karolinska Institute, Söder Hospital, Stockholm, and the Department of Clinical Pharmacology at the Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.

Arch Neurol. 1984;41(8):830-834. doi:10.1001/archneur.1984.04050190036011

• Fluctuations in plasma carbamazepine concentrations were related to side effects in five epileptics. One patient was receiving only carbamazepine; four were receiving carbamazepine plus phenobarbital sodium or phenytoin sodium. The patients were studied during two 12-hour periods: carbamazepine given (1) twice daily or (2) four times daily. Concomitant medication regimens were kept constant; administration was single-blind. Plasma concentrations of carbamazepine, carbamazepine's epoxide metabolite, phenobarbital, and phenytoin were determined hourly; side effects were assessed simultaneously. Fluctuations in carbamazepine concentrations were 79% ± 29% higher than trough levels on a twice-daily dosage schedule and 40% ± 13% higher during four-times-a-day administration. The appearance and intensity of side effects followed the fluctuations in carbamazepine levels and were thus substantially reduced during the four-times-daily regimen. The intrapatient reproducibility of the side effects was good, whereas the thresholds of carbamazepine concentrations at which side effects appeared ranged from 17 to 37 μmole/L.