Carbamazepine and its metabolites in neuralgias: concentration-effect relations.
The aim of this study was to investigate the use of carbamazepine in the treatment of neuralgic pain and to determine a therapeutic plasma concentration range for carbamazepine in neuralgias. The relation between plasma concentration and the response to treatment (reduction in pain) was examined by logistic regression analysis of carbamazepine and its metabolites, the epoxide, the diol, and 2-hydroxycarbamazepine. The plasma concentrations of carbamazepine, the epoxide, and the diol were significantly related to the probability of a 25% reduction in pain. Only carbamazepine was significantly related to the probability of 50% and 75% pain reduction. However, multiple regression analysis with backward elimination of the data showed a significant correlation between both carbamazepine and the epoxide with regard to the probability of 50% and 75% reductions in pain. This confirms the previous finding that the epoxide has antineuralgic properties [Tomson and Bertilsson 1984]. The therapeutic plasma concentration range for carbamazepine in neuralgias, defined as the range of concentrations that would be expected to provide a 25-75% reduction in pain in 50% of patients, was 2-7 micrograms.ml-1 (HPLC) or 5-17 micrograms.ml-1 (EMIT).
Moosa
R S
RS
Department of Pharmacology, University of Durban-Westville, South Africa.
McFadyen
M L
ML
Miller
R
R
Rubin
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D017248:Enzyme Multiplied Immunoassay Technique; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D012044:Regression Analysis
D002220:Carbamazepine; C004822:10,11-dihydro-10,11-dihydroxy-5H-dibenzazepine-5-carboxamide; C056205:2-hydroxycarbamazepine; C012227:carbamazepine epoxide