Interdosage fluctuations in plasma carbamazepine concentration determine intermittent side effects
T. Tomson
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 mumole/L.
