Effect of acute doses of controlled-release carbamazepine on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function.
The neurotoxic effect of acute doses of carbamazepine controlled-release (CBZ-CR) divitabs (800, 1,200, and 1,600 mg) was assessed on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function in 10 healthy volunteers in a double-blind, randomised, placebo-controlled, phase I study. Significant changes compared to placebo were demonstrated for the clinical scales, ataxia (AT), convergence of the near-point (CNP), peak saccadic velocity (PSV), critical flicker fusion (CFF), spectral analysis of the EEG, and brainstem auditory evoked potential (BAEP) tests. Digit repetition, digit symbol substitution, Sternberg memory scanning time, Sternberg choice reaction time, saccadic latency, and saccadic accuracy showed important negative findings. Significant clinical tolerance to side effects developed within 20 to 33 h after CBZ-CR dosage during a period in which the mean CBZ blood levels remained virtually unchanged. CBZ-CR, 800, 1,200, and 1,600 mg yielded low, medium, and high therapeutic blood levels, respectively, for +10 to +33 h after dosage without the development of severe clinical side effects.
van der Meyden
C H
CH
Department of Neurology, University of Pretoria, South Africa.
Bartel
P R
PR
Sommers
D K
DK
Blom
M
M
Becker
P
P
Erasmus
S
S
Griesel
D
D
D000328:Adult; D001921:Brain / Q000187:drug effects*; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D004585:Electrooculography / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005133:Eye Movements / Q000187:drug effects; D005425:Flicker Fusion / Q000187:drug effects; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D010919:Placebos; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D003692:Delayed-Action Preparations; D010919:Placebos; D002220:Carbamazepine