Pharmacokinetics and cognitive effects of carbamazepine formulations with different dissolution rates.
OBJECTIVE
In this study our aim was to assess pharmacokinetic effects and adverse cognitive effects of switches between generic and branded formulations of carbamazepine (CBZ).


METHODS
Twelve patients were included in a randomized open-label, observer-blind, cross-over design with a double-baseline period, comparing three different formulations of carbamazepine in monotherapy--the innovatory branded form Tegretol and two generic forms, CBZ Pharmachemie and CBZ Pharbita. Cognitive assessment was carried out at baseline and 3 days after a cross-over.


RESULTS
Area under the curve and a number of pharmacokinetic properties (serum concentration day curves, change in serum concentration (delta scores), peak/trough concentrations and peak time) did not differ among the three CBZ formulations. Therefore, the basic assumption for this study, i.e. to test pharmacokinetic-related differences in cognitive profile, was not met. In line with these findings, none of the cognitive variables showed statistically significant differences with respect to the cognitive profile during the day.


CONCLUSIONS
Switches between the investigated generic CBZ formulations and the branded product did not result in any difference in cognitive profiles. These results are not necessarily valid, though, for other generic forms of CBZ, for other types of antiepileptic drugs or for CBZ treatment in higher doses or in polytherapy.
Aldenkamp
A P
AP
Head Department of Behavioral Science, Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands.
Rentmeester
T
T
Hulsman
J
J
Majoie
M
M
Doelman
J
J
Diepman
L
L
Schellekens
A
A
Franken
M
M
Olling
M
M
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002220:Carbamazepine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D016568:Drugs, Generic; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D016037:Single-Blind Method; D012995:Solubility
D000927:Anticonvulsants; D016568:Drugs, Generic; D002220:Carbamazepine