Influence of long-term administration of anticonvulsants on human somatic chromosomes. Relationships of chromosome aberrations to plasma concentration, dosage and duration of anticonvulsants.
Chromosomal aberrations of 16 patients who have taken anticonvulsants for a long time were examined, and the following results were obtained. (1) There was no definite relation between the dosage of anticonvulsants and the incidence of abnormal cells, but positive correlation was recognized between the plasma concentration of the agents and the incidence of abnormal cells. (2) A significant correlation was recognized between the duration of administration and the incidence of abnormal cells. (3) The mean duration of drug administration was 16.9 years, with the incidence of abnormal cells of more than 15% in a group of 12 abnormal female subjects, and 8.1 years with an incidence of abnormal cells of less than 15% in a group of 9 normal subjects. (4) Morphological chromosome aberrations observed were mostly gaps and breaks. Any increase of exchange-type aberration was not recognized. It is conceivable that plasma factors might be more significant than the direct action from drugs as a mechanism of chromosome aberration. We speculate about the effects of lymphocyte chromosome aberration on living bodies, and the necessity of chromosome examination for the patients on long-term anticonvulsant therapy.
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy*; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants