Impairment of psychomotor function at modest plasma concentrations of carbamazepine after administration of the liquid suspension to naive subjects.
1. The influence of pharmaceutical formulation on the plasma drug concentration-time curve and the psychomotor responses to 400 mg carbamazepine has been assessed in 12 healthy male volunteers; three formulations and placebo were compared in a randomised, blind, crossover study. 2. The plasma concentration of carbamazepine rose to a maximum of 3-7 mg l-1 by 2-3 h after administration of the liquid suspension. Conventional and controlled release tablet formulations gave lower peaks at about 8 and 32 h, respectively. From 32 h onwards the plasma concentrations from the three formulations were indistinguishable. 3. Significant impairment of psychomotor function was observed after the liquid suspension only; subjective sedation was significant at 1 and 2 h and the critical flicker fusion frequency threshold was lowered at 1-8 h. Digit-symbol substitution, choice reaction time and body sway gave less conclusive evidence of impairment. 4. The results do not support the hypothesis that a psychomotor effect from carbamazepine is a threshold phenomenon with a critical plasma drug concentration at about 8 mg l-1. 5. A second hypothesis that rate of rise of plasma carbamazepine concentration has an important influence on psychomotor effect fits the observations. This interpretation is tentative since the use of a fixed dose of carbamazepine meant that differences due to rate of rise of drug concentration were confounded with differences due to peak height.
Wildin
J D
JD
Department of Physiological Sciences, University of Manchester.
Pleuvry
B J
BJ
Mawer
G E
GE
D000328:Adult; D001259:Ataxia / Q000139:chemically induced; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D005425:Flicker Fusion / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects*; D013535:Suspensions
D013535:Suspensions; D002220:Carbamazepine