Steady state concentrations and diurnal fluctuations of carbamazepine in patients after different slow release formulations.
The bioavailability and serum level fluctuations of three carbamazepine (CBZ, CAS 298-46-4) slow release preparations marketed in Germany were compared in patients with epilepsy. Ten patients who were on CBZ monotherapy and had reached a steady state with morning trough levels above 10 micrograms/ml received all 3 preparations in sequential 3-day periods. On the 3rd day of each period, a 24-h serum drug level profile was determined. Only minimal differences could be found. One preparation had a significantly higher AUC than one of the others (p less than 0.05), and this difference seemed to be correlated with higher fluctuations of serum levels and, especially, an increased Cmax. Although the group differences are minimal, more important differences could be observed individually. One patient had, with one of the three preparations, a reduction in seizure frequency but simultaneously developed important signs and symptoms of toxicity. It is concluded that all 3 preparations are equally suitable for chronic antiepileptic drug treatment. In a well-controlled patient, however, interchange between preparations is not advisable as their kinetics in individual patients can be sufficiently different to cause toxicity or seizure relapse.
Wolf
P
P
Epilepsy Centre Bethel, Bielefeld, Fed. Rep. of Germany.
May
T
T
Tiska
G
G
Schreiber
G
G
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy
D003692:Delayed-Action Preparations; D002220:Carbamazepine